A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
May 23, 2026 updated by: National Cancer Institute (NCI)
A Phase 3 Trial Investigating Blinatumomab (NSC# 765986) in Combination With Chemotherapy in Patients With Newly Diagnosed Standard Risk or Down Syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients With Localized B-Lymphoblastic Lymphoma (B-LLy)
This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome.
Monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.
Chemotherapy drugs, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Leucovorin decreases the toxic effects of methotrexate.
Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells.
Giving blinatumomab and combination chemotherapy may work better than combination chemotherapy alone in treating patients with B-ALL.
This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment).
Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.
Study Overview
Status
Active, not recruiting
Intervention / Treatment
- Drug: Cyclophosphamide
- Drug: Mercaptopurine
- Drug: Vincristine Sulfate
- Drug: Doxorubicin Hydrochloride
- Drug: Dexamethasone
- Biological: Blinatumomab
- Radiation: Radiation Therapy
- Drug: Thioguanine
- Drug: Prednisone
- Drug: Leucovorin Calcium
- Drug: Cytarabine
- Drug: Asparaginase Erwinia chrysanthemi
- Drug: Mercaptopurine Oral Suspension
- Drug: Methotrexate
- Drug: Pegaspargase
- Drug: Prednisolone
- Radiation: Radiation Therapy
Detailed Description
PRIMARY OBJECTIVES:
I. To determine in a randomized manner if the addition of 2 cycles of blinatumomab to standard therapy improves disease-free survival (DFS) in patients with standard risk (SR) B-ALL and higher risk features (SR-High), and patients with standard-risk average (SR-Avg) B-ALL who are negative for minimal residual disease (MRD) by flow cytometry but have detectable or indeterminate MRD as measured by high-throughput sequencing (HTS) at end of induction (EOI).
II. To confirm that boys in the standard-risk favorable (SR-Fav) subset of B-ALL, with or without Down syndrome (DS), will maintain a 5-year DFS of greater than 93% when treated with a standard chemotherapy regimen with a treatment duration of 2 years from the start of interim maintenance I (IM1).
SECONDARY OBJECTIVES:
I. To describe the DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of IM1, regardless of sex.
II. To describe the DFS for patients with standard-risk favorable (SR-Fav) B-ALL when treated with a standard chemotherapy regimen.
III. To determine if patients with DS-High achieve a reduction of treatment-related mortality (TRM) after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of delayed intensification [DI]) with 3 cycles of blinatumomab.
IV. To describe the DFS characterized by the replacement of intensive elements of standard chemotherapy with 3 cycles of blinatumomab in patients with DS-High B ALL.
V. To describe the DFS for patients with localized (Murphy stage I and II) B lymphoblastic lymphoma (B-LLy) receiving standard risk B-ALL therapy.
VI. To compare the change in neurocognitive functioning, as measured by the CogState Cognitive Composite, from baseline to end-of-therapy among patients with ALL ages 4- < 10 years at the time of diagnosis between children from poor families (defined as presence of household material hardship [HMH], including either food, housing or energy insecurity) and non-poor families (absence of HMH).
VII. To describe the impact of blinatumomab on caregiver burden and patient/proxy-reported symptoms among a subset of children enrolled in the HMH and neurocognitive outcome study.
VII. To evaluate available peripheral blood (PB) samples at EOI using HTS MRD and compare the results against bone marrow (BM) results.
IX. To evaluate available end of Consolidation (EOC) BM samples using HTS in patients who were Day 29 MRD positive by flow cytometry and who have submitted EOC BM flow cytometry results.
EXPLORATORY OBJECTIVES:
I. To explore adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL.
II. To explore the impact of acute lymphoblastic leukemia (ALL) and its therapy on neurocognitive, functional, and quality of life outcomes in patients with DS and ALL, as measured by caregiver (parent/legal guardian) questionnaires.
III. To define the prevalence of minimal marrow disease (MMD) in B-LLy and to correlate MMD at diagnosis with outcome in patients with B-LLy.
IV. To explore the significance of and genomic landscape of Ig clonal composition in pediatric B-ALL.
V. To explore the incidence of HTS MRD ≥ 0.01% versus (vs.) HTS MRD < 0.01% in patients with multiparameter flow cytometry defined MRD < 0.01% at end of Induction and genetically characterize those with discordance defined by the 0.01% threshold.
VI. To test whether differences in cerebrospinal fluid (CSF) metabolites clustered in glycerophospholipid metabolic pathways will distinguish patients with vs. without neurocognitive decline.
VII. To determine the ability of next-generation sequencing assays to detect and track leukemic cell-free deoxyribonucleic acid (DNA) in CSF.
VIII. Using single-cell genomic profiling, describe intra-tumoral clonal heterogeneity and cell developmental state in National Cancer Institute (NCI) SR B-ALL patients and determine its relationship to immunoglobulin clonality and response to therapy.
OUTLINE: All patients are assigned to, and complete an INDUCTION treatment regimen. Patients are then assigned to a CONSOLIDATION treatment regimen. Finally, following CONSOLIDATION, patients are either assigned or randomized to 1 of 7 arms.
NON-DS SR B-ALL INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenous (IV) push over 1 minute on days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on days 1-28, pegaspargase IV over 1-2 hours or intramuscularly (IM) on day 4, and methotrexate IT on days 8 and 29. CNS2 patients also receive cytarabine IT twice weekly except during weeks when days 8 and 29 methotrexate is administered. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
* After Non-DS SR B-ALL INDUCTION, SR-Fav and SR-Avg patients complete SR CONSOLIDATION, while patients with SR-High complete high-risk (HR) CONSOLIDATION.
DS B-ALL INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and patients 10 years of age or older receive prednisone or prednisolone PO or IV BID on days 1-28. CNS2 patients also receive cytarabine IT twice weekly except during weeks when days 8 and 29 IT methotrexate is administered. CNS3 patients also receive methotrexate IT on days 15 and 22, and leucovorin PO or IV every 6 hours for 2 doses on days 16 and 23. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
* After DS B-ALL INDUCTION, patients without high risk features and MRD < 0.01 % complete SR CONSOLIDATION. Patients without high risk features and MRD >= 0.01%, OR with high risk features and any MRD complete HR CONSOLIDATION.
NON-DS B-LLy INDUCTION: Patients receive cytarabine IT on day 1 and twice weekly if CNS2, vincristine IV push over 1 minute on days 1, 8, 15, and 22, dexamethasone PO or IV BID on days 1-28, pegaspargase IV over 1-2 hours or IM on day 4, and methotrexate IT on days 8 and 29. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
* After NON-DS B-LLy INDUCTION, all B-LLy patients then complete SR CONSOLIDATION.
DS B-LLY INDUCTION: Patients receive cytarabine IT on day 1, vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and patients 10 years of age or older receive PO or IV prednisone or methylprednisolone on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
* After DS B-LLy INDUCTION, patients then complete SR CONSOLIDATION.
SR CONSOLIDATION: Patients receive vincristine IV push over 1 minute on day 1, mercaptopurine PO on days 1-28, and methotrexate IT on days 1, 8, and 15. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2, 9, and 16. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
* After SR CONSOLIDATION, patients with MRD undetectable are assigned to ARM A, and patients with MRD detectable/indeterminate/unavailable are randomized to ARM A or B. Patients with SR-Fav and all B-LLy patients are assigned to treatments identical to that in ARM A.
HR CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, vincristine IV push over 1 minute on days 15, 22, 43, and 50, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 , and pegaspargase IV over 1-2 hours or IM on days 15 and 43. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2, 9, 16, and 23 (on days 2 and 9 only for DS CNS3 patients). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity. Patients with continued clinical evidence of DS or testicular leukemia (from diagnosis through the end of Induction) undergo testicular radiation therapy over 12 fractions once daily (QD).
* After HR CONSOLIDATION, patients are randomized to ARM C or D. DS B-ALL patients with MRD < 1% are assigned to an arm including three blocks of blinatumomab.
ARM A:
- INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV push over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and 36-39. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE II: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes undiluted or 10-15 minutes diluted on days 1, 11, 21, 31, and 41, and methotrexate IT on days 1 and 31. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- MAINTENANCE: Non-DS patients receive methotrexate IT on day 1, vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. DS patients receive vincristine IV push over 1 minute on day 1, methotrexate IT on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78, and leucovorin IV or PO on day 2 if DS. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of INTERIM MAINTENANCE I is reached in the absence of disease progression or unacceptable toxicity.
ARM B:
- BLINATUMOMAB BLOCK I: Patients receive dexamethasone IV or PO on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive leucovorin IV or PO every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- BLINATUMOMAB BLOCK II: Patients receive methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
- DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1 and 29, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV push over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE II: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- MAINTENANCE: Non-DS patients receive methotrexate IT on day 1 (omit cycles 5-6), vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 1 when coinciding with IT methotrexate). DS patients receive methotrexate IT on day 1 (omit cycles 5-6), dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 1 when coinciding with IT methotrexate), for DS patients and leucovorin IV or PO every 6 hours for 2 doses on day 2 (omit on final 2 cycles). Treatment repeats every 84 days until a total duration of therapy of 2 years from start of INTERIM MAINTENANCE I is reached in the absence of disease progression or unacceptable toxicity.
ARM C:
- INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on day 1 and 29, and leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV over 1 minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE II: Patients receive vincristine IV over 1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5 minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- MAINTENANCE: Patients receive vincristine IV over 1 minute on day 1, prednisone or prednisolone or methylprednisolone PO or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on days 1 and 29 of cycles 1-2 and on day 1 of subsequent cycles, methotrexate PO on days 8, 15, 22, 29 (for cycle 3 and later only), 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.
ARM D:
- BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days 1-28. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE I: Patients receive vincristine IV over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56, methotrexate IT on days 1 and 29, and leucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
- DELAYED INTENSIFICATION: Patients receive methotrexate IT on day 1, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV over 1 minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE II: Patients receive vincristine IV over 1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5 minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on days 2 and 22. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- MAINTENANCE: Patients receive methotrexate IT on day 1, vincristine IV over 1 minute on day 1, prednisone, prednisolone or methylprednisolone PO or IV on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.
DS-HIGH B-ALL:
- BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or IV on day 1, blinatumomab IV continuously on days 1-28, methotrexate IT on day 1 (or on day 56 of Consolidation), and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE: Patients receive vincristine IV push over 1 minute on days 1, 15, 29, and 43, intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-46, methotrexate IT on days 1 and 29, and leucovorin PO or IV every 6 hours for 2 doses on days 2-4, 16-18, 30-32, and 44-46. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.
- BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
- DELAYED INTENSIFICATION: Patients receive vincristine IV over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate IT on day 1, leucovorin PO or IV every 6 hours for 2 doses on day 2, and pegaspargase IV over 1-2 hours or IM on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.
- BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.
- MAINTENANCE: Patients receive vincristine IV push over 1 minute on day 1, prednisone, prednisolone or methylprednisolone PO or IV BID on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on day 1, methotrexate PO on days 8, 15, 22, 29 (omit day 29 for first 3 cycles for patients who do not receive cranial radiotherapy), 36, 43, 50, 57, 64, 71, and 78, and leucovorin PO on days 2 and 30 (day 30 dose is for cycles 1-3 and for patients who do not receive cranial radiotherapy). CNS3 patients receive cranial radiotherapy during first 4 weeks of cycle 1. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.
All B-LLy patients:
- INTERIM MAINTENANCE I: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- DELAYED INTENSIFICATION: Patients receive vincristine IV push over 1 minute on days 1, 8 and 15, doxorubicin IV over 1-15 minutes on days 1, 8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate IT on days 1 and 29, pegaspargase IV over 1-2 hours or IM on day 4, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients additionally receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- INTERIM MAINTENANCE II: Patients receive vincristine IV push over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.
- MAINTENANCE: Patients receive vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on day 1, and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of interim maintenance I is reached in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 weeks until complete blood count(CBC)/differential/platelet count recovery, then every 3 months for the first 2 years, then every 4-6 months for the 3rd year, and every 6-12 months for the 4th and 5th years.
Study Type
Interventional
Enrollment (Estimated)
6720
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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New South Wales
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Hunter Regional Mail Centre, New South Wales, Australia, 2310
- John Hunter Children's Hospital
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Westmead, New South Wales, Australia, 2145
- The Children's Hospital at Westmead
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Queensland
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South Brisbane, Queensland, Australia, 4101
- Queensland Children's Hospital
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South Australia
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North Adelaide, South Australia, Australia, 5006
- Women's and Children's Hospital-Adelaide
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Victoria
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Clayton, Victoria, Australia, 3168
- Monash Medical Center-Clayton Campus
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Parkville, Victoria, Australia, 3052
- Royal Children's Hospital
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Western Australia
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Perth, Western Australia, Australia, 6009
- Perth Children's Hospital
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Québec, Canada, G1V 4G2
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
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Alberta
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Calgary, Alberta, Canada, T3B 6A8
- Alberta Children's Hospital
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Edmonton, Alberta, Canada, T6G 2B7
- University of Alberta Hospital
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British Columbia
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Vancouver, British Columbia, Canada, V6H 3V4
- British Columbia Children's Hospital
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Manitoba
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Winnipeg, Manitoba, Canada, R3E 0V9
- CancerCare Manitoba
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Canada, A1B 3V6
- Janeway Child Health Centre
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3K 6R8
- IWK Health Centre
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Ontario
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Hamilton, Ontario, Canada, L8N 3Z5
- McMaster Children's Hospital at Hamilton Health Sciences
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Kingston, Ontario, Canada, K7L 2V7
- Kingston Health Sciences Centre
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London, Ontario, Canada, N6A 5W9
- Children's Hospital
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Ottawa, Ontario, Canada, K1H 8L1
- Children's Hospital of Eastern Ontario
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Toronto, Ontario, Canada, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Canada, H3H 1P3
- The Montreal Children's Hospital of the MUHC
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Sherbrooke, Quebec, Canada, J1H 5N4
- Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
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Saskatchewan
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Saskatoon, Saskatchewan, Canada, S7N 4H4
- Saskatoon Cancer Centre
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Saskatoon, Saskatchewan, Canada, S7N 0W8
- Jim Pattison Children's Hospital
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Christchurch, New Zealand, 8011
- Christchurch Hospital
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Auckland
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Grafton, Auckland, New Zealand, 1145
- Starship Children's Hospital
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Caguas, Puerto Rico, 00726
- HIMA San Pablo Oncologic Hospital
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San Juan, Puerto Rico, 00926
- University Pediatric Hospital
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Alabama
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Birmingham, Alabama, United States, 35233
- Children's Hospital of Alabama
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Mobile, Alabama, United States, 36604
- USA Health Strada Patient Care Center
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Alaska
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Anchorage, Alaska, United States, 99508
- Providence Alaska Medical Center
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Arizona
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Mesa, Arizona, United States, 85202
- Banner Children's at Desert
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Phoenix, Arizona, United States, 85016
- Phoenix Childrens Hospital
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Tucson, Arizona, United States, 85719
- Banner University Medical Center - Tucson
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Arkansas
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Little Rock, Arkansas, United States, 72202-3591
- Arkansas Children's Hospital
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California
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Downey, California, United States, 90242
- Kaiser Permanente Downey Medical Center
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Duarte, California, United States, 91010
- City of Hope Comprehensive Cancer Center
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Loma Linda, California, United States, 92354
- Loma Linda University Medical Center
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Long Beach, California, United States, 90806
- Miller Children's and Women's Hospital Long Beach
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Los Angeles, California, United States, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, United States, 90027
- Children's Hospital Los Angeles
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Los Angeles, California, United States, 90095
- Mattel Children's Hospital UCLA
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Madera, California, United States, 93636
- Valley Children's Hospital
-
Oakland, California, United States, 94609
- UCSF Benioff Children's Hospital Oakland
-
Oakland, California, United States, 94611
- Kaiser Permanente-Oakland
-
Orange, California, United States, 92868
- Children's Hospital of Orange County
-
Palo Alto, California, United States, 94304
- Lucile Packard Children's Hospital Stanford University
-
Sacramento, California, United States, 95816
- Sutter Medical Center Sacramento
-
Sacramento, California, United States, 95817
- University of California Davis Comprehensive Cancer Center
-
San Diego, California, United States, 92123
- Rady Children's Hospital - San Diego
-
San Diego, California, United States, 92134
- Naval Medical Center -San Diego
-
San Francisco, California, United States, 94158
- UCSF Medical Center-Mission Bay
-
Santa Barbara, California, United States, 93102
- Santa Barbara Cottage Hospital
-
Torrance, California, United States, 90502
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- Children's Hospital Colorado
-
Denver, Colorado, United States, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
-
-
Connecticut
-
Hartford, Connecticut, United States, 06106
- Connecticut Children's Medical Center
-
New Haven, Connecticut, United States, 06520
- Yale University
-
-
Delaware
-
Wilmington, Delaware, United States, 19803
- Alfred I duPont Hospital for Children
-
-
District of Columbia
-
Washington D.C., District of Columbia, United States, 20010
- Children's National Medical Center
-
Washington D.C., District of Columbia, United States, 20007
- MedStar Georgetown University Hospital
-
-
Florida
-
Fort Lauderdale, Florida, United States, 33316
- Broward Health Medical Center
-
Fort Myers, Florida, United States, 33908
- Golisano Children's Hospital of Southwest Florida
-
Gainesville, Florida, United States, 32610
- UF Health Cancer Institute - Gainesville
-
Hollywood, Florida, United States, 33021
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
-
Jacksonville, Florida, United States, 32207
- Nemours Children's Clinic-Jacksonville
-
Loxahatchee Groves, Florida, United States, 33470
- Palms West Radiation Therapy
-
Miami, Florida, United States, 33155
- Nicklaus Children's Hospital
-
Miami, Florida, United States, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
-
Miami, Florida, United States, 33176
- Miami Cancer Institute
-
Orlando, Florida, United States, 32827
- Nemours Children's Hospital
-
Orlando, Florida, United States, 32803
- AdventHealth Orlando
-
Orlando, Florida, United States, 32806
- Arnold Palmer Hospital for Children
-
Pensacola, Florida, United States, 32504
- Sacred Heart Hospital
-
St. Petersburg, Florida, United States, 33701
- Johns Hopkins All Children's Hospital
-
Tampa, Florida, United States, 33606
- Tampa General Hospital
-
Tampa, Florida, United States, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
-
West Palm Beach, Florida, United States, 33407
- Saint Mary's Medical Center
-
-
Georgia
-
Atlanta, Georgia, United States, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
-
Augusta, Georgia, United States, 30912
- Augusta University Medical Center
-
Macon, Georgia, United States, 31201
- Atrium Health Navicent
-
Savannah, Georgia, United States, 31404
- Memorial Health University Medical Center
-
-
Hawaii
-
Honolulu, Hawaii, United States, 96826
- Kapiolani Medical Center for Women and Children
-
Honolulu, Hawaii, United States, 96859
- Tripler Army Medical Center
-
-
Idaho
-
Boise, Idaho, United States, 83712
- Saint Luke's Cancer Institute - Boise
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- University of Chicago Comprehensive Cancer Center
-
Chicago, Illinois, United States, 60612
- University of Illinois
-
Chicago, Illinois, United States, 60611
- Lurie Children's Hospital-Chicago
-
Maywood, Illinois, United States, 60153
- Loyola University Medical Center
-
Oak Lawn, Illinois, United States, 60453
- Advocate Children's Hospital-Oak Lawn
-
Park Ridge, Illinois, United States, 60068
- Advocate Children's Hospital-Park Ridge
-
Peoria, Illinois, United States, 61637
- OSF Children's Hospital of Illinois
-
Springfield, Illinois, United States, 62702
- Southern Illinois University School of Medicine
-
Winfield, Illinois, United States, 60190
- Northwestern Medicine Central DuPage Hospital
-
-
Indiana
-
Indianapolis, Indiana, United States, 46202
- Riley Hospital for Children
-
Indianapolis, Indiana, United States, 46260
- Ascension Saint Vincent Indianapolis Hospital
-
-
Iowa
-
Des Moines, Iowa, United States, 50309
- Blank Children's Hospital
-
Iowa City, Iowa, United States, 52242
- University of Iowa/Holden Comprehensive Cancer Center
-
-
Kentucky
-
Lexington, Kentucky, United States, 40536
- University of Kentucky/Markey Cancer Center
-
Louisville, Kentucky, United States, 40202
- Norton Children's Hospital
-
-
Louisiana
-
New Orleans, Louisiana, United States, 70121
- Ochsner Medical Center Jefferson
-
New Orleans, Louisiana, United States, 70118
- Children's Hospital New Orleans
-
-
Maine
-
Bangor, Maine, United States, 04401
- Eastern Maine Medical Center
-
Scarborough, Maine, United States, 04074
- Maine Children's Cancer Program
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
Baltimore, Maryland, United States, 21215
- Sinai Hospital of Baltimore
-
Baltimore, Maryland, United States, 21201
- University of Maryland/Greenebaum Cancer Center
-
Bethesda, Maryland, United States, 20889-5600
- Walter Reed National Military Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02215
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital Cancer Center
-
Boston, Massachusetts, United States, 02111
- Tufts Children's Hospital
-
Springfield, Massachusetts, United States, 01199
- Baystate Medical Center
-
Worcester, Massachusetts, United States, 01655
- UMass Memorial Medical Center - University Campus
-
-
Michigan
-
Ann Arbor, Michigan, United States, 48109
- C S Mott Children's Hospital
-
Detroit, Michigan, United States, 48201
- Children's Hospital of Michigan
-
Detroit, Michigan, United States, 48236
- Henry Ford Health Saint John Hospital
-
East Lansing, Michigan, United States, 48823
- Michigan State University
-
Grand Rapids, Michigan, United States, 49503
- Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
-
Kalamazoo, Michigan, United States, 49007
- Bronson Methodist Hospital
-
Royal Oak, Michigan, United States, 48073
- Corewell Health Children's
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
-
Minneapolis, Minnesota, United States, 55455
- University of Minnesota/Masonic Cancer Center
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic in Rochester
-
-
Mississippi
-
Jackson, Mississippi, United States, 39216
- University of Mississippi Medical Center
-
-
Missouri
-
Columbia, Missouri, United States, 65212
- University of Missouri Children's Hospital
-
Kansas City, Missouri, United States, 64108
- Children's Mercy Hospitals and Clinics
-
St Louis, Missouri, United States, 63110
- Washington University School of Medicine
-
St Louis, Missouri, United States, 63141
- Mercy Hospital Saint Louis
-
St Louis, Missouri, United States, 63104
- Cardinal Glennon Children's Medical Center
-
-
Nebraska
-
Omaha, Nebraska, United States, 68198
- University of Nebraska Medical Center
-
Omaha, Nebraska, United States, 68114
- Children's Hospital and Medical Center of Omaha
-
-
Nevada
-
Las Vegas, Nevada, United States, 89144
- Summerlin Hospital Medical Center
-
Las Vegas, Nevada, United States, 89109
- Sunrise Hospital and Medical Center
-
Las Vegas, Nevada, United States, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
-
Las Vegas, Nevada, United States, 89102
- University Medical Center of Southern Nevada
-
Reno, Nevada, United States, 89502
- Renown Regional Medical Center
-
-
New Hampshire
-
Lebanon, New Hampshire, United States, 03756
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
-
-
New Jersey
-
Hackensack, New Jersey, United States, 07601
- Hackensack University Medical Center
-
Morristown, New Jersey, United States, 07960
- Morristown Medical Center
-
Neptune City, New Jersey, United States, 07753
- Jersey Shore Medical Center
-
New Brunswick, New Jersey, United States, 08901
- Saint Peter's University Hospital
-
New Brunswick, New Jersey, United States, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
-
Newark, New Jersey, United States, 07112
- Newark Beth Israel Medical Center
-
Paterson, New Jersey, United States, 07503
- Saint Joseph's Regional Medical Center
-
-
New Mexico
-
Albuquerque, New Mexico, United States, 87106
- Presbyterian Hospital
-
Albuquerque, New Mexico, United States, 87106
- University of New Mexico Cancer Center
-
-
New York
-
Albany, New York, United States, 12208
- Albany Medical Center
-
Brooklyn, New York, United States, 11219
- Maimonides Medical Center
-
Mineola, New York, United States, 11501
- NYU Langone Hospital - Long Island
-
New Hyde Park, New York, United States, 11040
- The Steven and Alexandra Cohen Children's Medical Center of New York
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, United States, 10029
- Mount Sinai Hospital
-
New York, New York, United States, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, United States, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, United States, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Rochester, New York, United States, 14642
- University of Rochester
-
Stony Brook, New York, United States, 11794
- Stony Brook University Medical Center
-
Syracuse, New York, United States, 13210
- State University of New York Upstate Medical University
-
The Bronx, New York, United States, 10467
- Montefiore Medical Center - Moses Campus
-
Valhalla, New York, United States, 10595
- New York Medical College
-
-
North Carolina
-
Asheville, North Carolina, United States, 28801
- Mission Hospital
-
Chapel Hill, North Carolina, United States, 27599
- UNC Lineberger Comprehensive Cancer Center
-
Charlotte, North Carolina, United States, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Charlotte, North Carolina, United States, 28204
- Novant Health Presbyterian Medical Center
-
Durham, North Carolina, United States, 27710
- Duke University Medical Center
-
Greenville, North Carolina, United States, 27834
- East Carolina University
-
Winston-Salem, North Carolina, United States, 27157
- Wake Forest University Health Sciences
-
-
North Dakota
-
Fargo, North Dakota, United States, 58122
- Sanford Broadway Medical Center
-
-
Ohio
-
Akron, Ohio, United States, 44308
- Children's Hospital Medical Center of Akron
-
Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Foundation
-
Cleveland, Ohio, United States, 44106
- Rainbow Babies and Childrens Hospital
-
Columbus, Ohio, United States, 43205
- Nationwide Children's Hospital
-
Dayton, Ohio, United States, 45404
- Dayton Children's Hospital
-
Toledo, Ohio, United States, 43606
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
-
-
Oklahoma
-
Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma Health Sciences Center
-
Tulsa, Oklahoma, United States, 74136
- Natalie Warren Bryant Cancer Center at Saint Francis
-
-
Oregon
-
Portland, Oregon, United States, 97239
- Oregon Health and Science University
-
Portland, Oregon, United States, 97227
- Legacy Emanuel Children's Hospital
-
-
Pennsylvania
-
Allentown, Pennsylvania, United States, 18103
- Lehigh Valley Hospital-Cedar Crest
-
Danville, Pennsylvania, United States, 17822
- Geisinger Medical Center
-
Hershey, Pennsylvania, United States, 17033
- Penn State Children's Hospital
-
Philadelphia, Pennsylvania, United States, 19104
- Children's Hospital of Philadelphia
-
Philadelphia, Pennsylvania, United States, 19134
- Saint Christopher's Hospital for Children
-
Pittsburgh, Pennsylvania, United States, 15224
- Children's Hospital of Pittsburgh of UPMC
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425
- Medical University of South Carolina
-
Columbia, South Carolina, United States, 29203
- Prisma Health Richland Hospital
-
Greenville, South Carolina, United States, 29605
- BI-LO Charities Children's Cancer Center
-
-
South Dakota
-
Sioux Falls, South Dakota, United States, 57117-5134
- Sanford USD Medical Center - Sioux Falls
-
-
Tennessee
-
Chattanooga, Tennessee, United States, 37403
- T C Thompson Children's Hospital
-
Knoxville, Tennessee, United States, 37916
- East Tennessee Childrens Hospital
-
Nashville, Tennessee, United States, 37232
- Vanderbilt University/Ingram Cancer Center
-
Nashville, Tennessee, United States, 37203
- The Children's Hospital at TriStar Centennial
-
-
Texas
-
Amarillo, Texas, United States, 79106
- Texas Tech University Health Sciences Center-Amarillo
-
Austin, Texas, United States, 78723
- Dell Children's Medical Center of Central Texas
-
Corpus Christi, Texas, United States, 78411
- Driscoll Children's Hospital
-
Dallas, Texas, United States, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Dallas, Texas, United States, 75230
- Medical City Dallas Hospital
-
El Paso, Texas, United States, 79905
- El Paso Children's Hospital
-
Fort Worth, Texas, United States, 76104
- Cook Children's Medical Center
-
Houston, Texas, United States, 77030
- M D Anderson Cancer Center
-
Houston, Texas, United States, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
-
Lubbock, Texas, United States, 79410
- Covenant Children's Hospital
-
Lubbock, Texas, United States, 79415
- UMC Cancer Center / UMC Health System
-
McAllen, Texas, United States, 78503
- Vannie Cook Children's Clinic
-
San Antonio, Texas, United States, 78229
- University of Texas Health Science Center at San Antonio
-
San Antonio, Texas, United States, 78207
- Children's Hospital of San Antonio
-
San Antonio, Texas, United States, 78229
- Methodist Children's Hospital of South Texas
-
Temple, Texas, United States, 76508
- Scott and White Memorial Hospital
-
-
Utah
-
Salt Lake City, Utah, United States, 84113
- Primary Children's Hospital
-
-
Vermont
-
Burlington, Vermont, United States, 05405
- University of Vermont and State Agricultural College
-
-
Virginia
-
Charlottesville, Virginia, United States, 22908
- University of Virginia Cancer Center
-
Falls Church, Virginia, United States, 22042
- Inova Fairfax Hospital
-
Norfolk, Virginia, United States, 23507
- Children's Hospital of The King's Daughters
-
Portsmouth, Virginia, United States, 23708-2197
- Naval Medical Center - Portsmouth
-
Richmond, Virginia, United States, 23298
- VCU Massey Comprehensive Cancer Center
-
Roanoke, Virginia, United States, 24014
- Carilion Children's
-
-
Washington
-
Seattle, Washington, United States, 98105
- Seattle Children's Hospital
-
Spokane, Washington, United States, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
-
Tacoma, Washington, United States, 98405
- Mary Bridge Children's Hospital and Health Center
-
Tacoma, Washington, United States, 98431
- Madigan Army Medical Center
-
-
West Virginia
-
Charleston, West Virginia, United States, 25304
- West Virginia University Charleston Division
-
Huntington, West Virginia, United States, 25701
- Edwards Comprehensive Cancer Center
-
Morgantown, West Virginia, United States, 26506
- West Virginia University Healthcare
-
-
Wisconsin
-
Green Bay, Wisconsin, United States, 54301
- Saint Vincent Hospital Cancer Center Green Bay
-
Madison, Wisconsin, United States, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
-
Marshfield, Wisconsin, United States, 54449
- Marshfield Medical Center-Marshfield
-
Milwaukee, Wisconsin, United States, 53226
- Children's Hospital of Wisconsin
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 year to 31 years (Child, Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- All B-ALL patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to treatment and enrollment on AALL1731. APEC 14B1 is not a requirement for B-LLy patients. B-LLy patients may directly enroll on AALL1731.
Age at diagnosis:
- Patients must be >= 365 days and < 10 years of age (B-ALL patients without DS).
- Patients must be >= 365 days and =< 31 years of age (B-ALL patients with DS).
- Patients must be >= 365 days and =< 31 years of age (B-LLy patients with or without DS).
- B-ALL patients without DS must have an initial white blood cell count < 50,000/uL (performed within 7 days prior to enrollment).
- B-ALL patients with DS are eligible regardless of the presenting white blood cell count (WBC) (performed within 7 days prior to enrollment).
Patient has newly diagnosed B-cell ALL, with or without Down syndrome: > 25% blasts on a bone marrow (BM) aspirate;
- OR if a BM aspirate is not obtained or is not diagnostic of B-ALL, the diagnosis can be established by a pathologic diagnosis of B-ALL on a BM biopsy;
- OR a complete blood count (CBC) documenting the presence of at least 1,000/uL circulating leukemic cells;
- OR patient has newly diagnosed B-cell LLy Murphy stages I or II, with or without Down syndrome.
- Note: For B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e., paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted (diagnostic biopsy for B-LLy must be performed within 14 days prior to enrollment).
- All patients and/or their parents or legal guardians must sign a written informed consent.
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Exclusion Criteria:
- Patient must not have secondary ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy. Note: patients with Down syndrome with a prior history of transient myeloproliferative disease (TMD) are not considered to have had a prior malignancy. They would therefore be eligible whether or not the TMD was treated with cytarabine.
- With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B ALL or B LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL1731.
For patients receiving steroid pretreatment, the following additional exclusion criteria apply:
- Non-DS B-ALL patients must not have received steroids for more than 24 hours in the 2 weeks prior to diagnosis without a CBC obtained within 3 days prior to initiation of the steroids.
- DS and non-DS B-LLy patients must not have received > 48 hours of oral or IV steroids within 4 weeks of diagnosis.
- Patients who have received > 72 hours of hydroxyurea within 1 week (7 days) prior to the start of systemic protocol therapy.
- B-ALL patients who do not have sufficient diagnostic bone marrow submitted for APEC14B1 diagnostic testing and who do not have a peripheral blood sample submitted containing > 1,000/uL circulating leukemia cells.
- Patient must not have acute undifferentiated leukemia (AUL).
Non-DS B-ALL patients with central nervous system [CNS]3 leukemia (CNS status must be known prior to enrollment).
- Note: DS patients with CNS3 disease are eligible but will be assigned to the DS-High B-ALL arm. CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment.
- Non-DS B-ALL patients with testicular leukemia. (Note: DS patients with testicular disease are eligible but will be assigned to the DS-High B-ALL arm).
For LLy patients, the following additional exclusion criteria apply:
- T-Lymphoblastic Lymphoma.
- Morphologically unclassifiable lymphoma.
- Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma.
- CNS positive disease or testicular involvement.
- M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow.
- Patients with known Charcot-Marie-Tooth disease.
- Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype.
- Patients requiring radiation at diagnosis.
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
- Lactating females who plan to breastfeed their infants.
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: Arm A (SR-Avg control)
Arm A: See detailed description.
|
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given PO or IV
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
|
|
Experimental: Arm B (SR-Avg experimental)
Arm B: See detailed description.
|
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
|
|
Active Comparator: Arm C (SR-High Control)
Arm C: See detailed description.
|
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given PO or IV
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO or IV
Other Names:
|
|
Experimental: Arm D (SR-High experimental)
Arm D See detailed description.
|
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given PO or IV
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO or IV
Other Names:
|
|
Experimental: B-LLy
See detailed description.
|
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given PO or IV
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO or IV
Other Names:
|
|
Experimental: DS B-ALL
See detailed description.
|
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Undergo cranial radiation therapy
Other Names:
Given PO
Other Names:
Given PO or IV
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Undergo testicular radiation therapy
Other Names:
|
|
Experimental: NCI SR or HR DS B-ALL
See detailed description.
|
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Given IV
Other Names:
Given PO or IV
Other Names:
Given PO or IV
Other Names:
Given IV or IM
Other Names:
Given PO
Other Names:
Given IT or IV
Other Names:
Given IV or IM
Other Names:
Given PO or IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Disease free survival (DFS) in randomization eligible patients with higher risk features (SR-High) or standard risk average (SR-Avg) B-ALL patients based on randomization with addition of blinatumomab
Time Frame: 5.3 years
|
Will be assessed in SR-High patients and SR-Avg B-ALL patients who are negative for MRD by flow cytometry but have detectable or indeterminate MRD as measured by high throughput sequencing (HTS) at end of induction (EOI), and patients with double trisomy of chromosomes 4 and 10 (DT) with MRD (flow) 0.01% - < 0.1%.
DFS is calculated as the time from randomization at the end of consolidation to first event (relapse, second malignancy, remission death) or censored at date of last contact.
Five year DFS estimates will be calculated from the point of randomization for both groups.
Two-sided 95% confidence intervals will be calculated.
|
5.3 years
|
|
DFS in boys in the SR-favorable subset of SR B-ALL with or without Down syndrome (DS)
Time Frame: 5.1 years
|
DFS is calculated as the time from end of induction to first event (relapse, second malignancy, remission death) or censored at date of last contact.
A five year DFS estimate and two-sided 80% confidence interval will be calculated.
|
5.1 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of interim maintenance (IM)1, regardless of sex
Time Frame: 5.1 years
|
DFS is calculated as the time from end of induction to first event (relapse, second malignancy, remission death) or censored at date of last contact.
A five year DFS estimate and a two-sided 95% confidence interval will be calculated.
|
5.1 years
|
|
DFS for patients with standard-risk favorable (SR-Fav) B-ALL when treated with a standard chemotherapy regimen
Time Frame: 5.1 years
|
DFS is calculated as the time from end of induction to first event (relapse, second malignancy, remission death) or censored at date of last contact.
A five year DFS estimate and a two-sided 95% confidence interval will be calculated.
|
5.1 years
|
|
Treatment-related mortality in Down syndrome high risk (DS-high) patients after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of DI) with 3 cycles of blinatumomab
Time Frame: 2.3 years
|
Percent of DS-high patients with treatment related mortalities will be reported with 95% confidence interval.
|
2.3 years
|
|
DFS of DS-High B-ALL patients when intensive elements of chemotherapy are replaced with 3 cycles of blinatumomab
Time Frame: 5.3 years
|
DFS is calculated as the time from the end of consolidation to first event (relapse, second malignancy, remission death) or censored at date of last contact.
A five year DFS estimate and a two-sided 80% confidence interval will be calculated.
|
5.3 years
|
|
DFS of patients with localized B-lymphoblastic lymphoma (B-LLy) receiving standard risk acute lymphoblastic leukemia therapy
Time Frame: 5 years
|
DFS is calculated as the time from study enrollment to first event (disease progression, relapse, second malignancy, remission death) or censored at date of last contact.
A five year DFS estimate and a two-sided 95% confidence interval will be calculated.
|
5 years
|
|
Change in neurocognitive functioning from baseline to end-of-therapy between children from poor (defined as presence of household material hardship [HMH], including either food, housing or energy insecurity) and non-poor families (absence of HMH)
Time Frame: 3.3 years
|
Neurocognitive functioning will be measured by the CogState Cognitive Composite at end of induction therapy and at follow-up one year off-therapy among patients with ALL ages 4-< 10 years at the time of diagnosis.
Mean and 95% confidence interval for change scores will be reported by HMH group.
|
3.3 years
|
|
Caregiver burden as measured by the Mean Total score from the Care of My Child with Cancer questionnaire among a subset of children enrolled in the HMH and neurocognitive outcome study
Time Frame: 1 year
|
The Mean Total score from the Care of My Child with Cancer questionnaire from end of Maintenance Cycle 1. Mean scores and 95% confidence intervals will be reported by randomization group.
|
1 year
|
|
Caregiver burden as measured by the At-Work Productivity Loss summary score from the Caregiver Work Limitations questionnaire among a subset of children enrolled in the HMH and neurocognitive outcome study
Time Frame: 1 year
|
The Mean Total score from the Care of My Child with Cancer questionnaire from end of Maintenance Cycle 1. Mean scores and 95% confidence intervals will be reported by randomization group.
|
1 year
|
|
Peripheral blood (PB) samples using HTS MRD vs. bone marrow (BM) results at EOI
Time Frame: 1 year
|
Will use the Kendall's Tau-b rank correlation coefficient accounting for the left censoring inherent to sensitivity of the method.
A high positive value would be strong evidence that the PB retains the relative information contained in the BM readings.
An estimate and two-sided 95% Confidence interval will be calculated using banked SR-Average and SR-High samples at EOI.
|
1 year
|
|
BM using HTS MRD vs. BM by flow cytometry at EOC in patients who were Day 29 MRD positive by flow cytometry
Time Frame: 1 year
|
Will use the Kendall's Tau-b rank correlation coefficient accounting for the left censoring inherent to sensitivity of the methods30.
A high positive value would be strong evidence that HTS of IgH loci determined-MRD from the BM at EOC retains the relative information contained in the flow-cytometry-determined readings.
An estimate and 95% Confidence interval will be calculated using pairs of banked samples at EOC.
|
1 year
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
To explore adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL
Time Frame: 5 years
|
FlowSom high resolution clustering approach to identify cellular subsets and/or activation states (endophenotypes) that distinguish cases from controls.
Perform secondary analysis using the "diffCyt" framework to identify those cell clusters that differ significantly between groups.
|
5 years
|
|
Neurocognitive, functional, and quality of life outcomes in patients with DS and ALL
Time Frame: 5 years
|
Measured by caregiver (parent/legal guardian) using questionnaires that rate executive function, behavior, adaptive skills, and quality of life.
|
5 years
|
|
Prevalence of minimal marrow disease (MMD) in B-LLy
Time Frame: 5 years
|
Correlate MMD at diagnosis with outcome in patients with B-LLy.
|
5 years
|
|
Genetic landscape of B-ALL lacking a clonal Ig sequence
Time Frame: 5 years
|
Will be measured by performing targeted sequencing (hemoglobin [heme] deoxyribonucleic acid [DNA] mutation and ribonucleic acid [RNA] fusion panels) on samples from all identified patients without a clonal Ig sequence with banked material and compare to matched subjects with clonal Ig sequences.
Will determine associations between having or lacking a clonal Ig sequence and discrete mutations/fusions using Fisher's exact test.
Will also be assessed with a 1-sided alpha of 0.05, a log-rank test.
|
5 years
|
|
Association between flow cytometry
Time Frame: At the end of induction
|
Will be determined by MRD and HTS of IgH loci from the BM in NCI SR B-ALL patients who are MRD positive by flow cytometry.
Will use the Kendall's Tau-b rank correlation coefficient accounting for the left censoring inherent to sensitivity of the methods.
A high positive value would be strong evidence that the PB retains the relative information contained in the BM readings.
An estimate and two-sided 95% Confidence interval will be calculated using banked SR-Average and SR-High samples.
|
At the end of induction
|
|
Differences in cerebrospinal fluid (CSF) metabolites clustered in glycerophospholipid metabolic pathways will distinguish patients with versus without neurocognitive decline
Time Frame: Up to 5 years
|
The metabolic composition of CSF will be analyzed using liquid chromatography/multiple-stage mass spectrometry.
Pathway analysis will be used to test whether the set of metabolites that best discriminate between groups are enriched within glycerophospholipid metabolic pathways.
Discriminant analysis and dimensionality reduction will be used to cluster samples.
Receiver operating curve analysis will be used to characterize the performance of the clustering algorithm.
|
Up to 5 years
|
|
Ability of next-generation sequencing assays to detect and track leukemic cell-free deoxyribonucleic acid (cfDNA) in cerebrospinal fluid
Time Frame: Up to 5 years
|
Will describe the frequency of detectable leukemic cfDNA in end of induction and consolidation CSF samples and compare the levels detected by each method.
We will also compare patterns of detectable leukemic cfDNA between patients who did and did not experience a subsequent relapse involving the CNS.
|
Up to 5 years
|
|
Intra-tumoral clonal heterogeneity and cell developmental state in NCI SR B-ALL patients and determine its relationship to immunoglobulin clonality and response to therapy
Time Frame: Up to 5 years
|
Will compare the cell developmental state of samples obtained from patients at diagnosis without a dominant recombined immunoglobulin (Ig) sequence to a matched cohort of those with one or more dominant Ig sequence(s) as determined by Ig high-throughput sequencing already performed on these samples.
|
Up to 5 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Sumit Gupta, Children's Oncology Group
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Sora F, Annunziata M, Laurenti L, Giammarco S, Chiusolo P, Innocenti I, Autore F, Metafuni E, Galli E, Bacigalupo A, Ferrara F, Sica S. Blinatumomab as a successful and safe therapy in Down syndrome patients with relapsed/refractory b-precursor acute lymphoblastic leukaemia: Case reports and literature review. Pediatr Blood Cancer. 2021 Jul;68(7):e29044. doi: 10.1002/pbc.29044. Epub 2021 Apr 12. No abstract available.
- Gupta S, Rau RE, Kairalla JA, Rabin KR, Wang C, Angiolillo AL, Alexander S, Carroll AJ, Conway S, Gore L, Kirsch I, Kubaney HR, Li AM, McNeer JL, Militano O, Miller TP, Moyer Y, O'Brien MM, Okada M, Reshmi SC, Shago M, Wagner E, Winick N, Wood BL, Haworth-Wright T, Zaman F, Zugmaier G, Zupanec S, Devidas M, Hunger SP, Teachey DT, Raetz EA, Loh ML. Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2025 Feb 27;392(9):875-891. doi: 10.1056/NEJMoa2411680. Epub 2024 Dec 7.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 3, 2019
Primary Completion (Estimated)
September 30, 2027
Study Completion (Estimated)
September 30, 2027
Study Registration Dates
First Submitted
April 12, 2019
First Submitted That Met QC Criteria
April 12, 2019
First Posted (Actual)
April 16, 2019
Study Record Updates
Last Update Posted (Actual)
May 27, 2026
Last Update Submitted That Met QC Criteria
May 23, 2026
Last Verified
April 1, 2026
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neurologic Manifestations
- Nervous System Diseases
- Neoplasms
- Genetic Diseases, Inborn
- Immune System Diseases
- Infections
- Virus Diseases
- Neoplasms by Histologic Type
- Neurobehavioral Manifestations
- Hematologic Diseases
- DNA Virus Infections
- Lymphatic Diseases
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Congenital Abnormalities
- Lymphoma, B-Cell
- Lymphoma
- Abnormalities, Multiple
- Intellectual Disability
- Leukemia, Lymphoid
- Leukemia
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Tumor Virus Infections
- Chromosome Disorders
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Hemic and Lymphatic Diseases
- Burkitt Lymphoma
- Down Syndrome
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
- Sulfur Compounds
- Organic Chemicals
- Heterocyclic Compounds, 1-Ring
- Heterocyclic Compounds
- Heterocyclic Compounds, 2-Ring
- Heterocyclic Compounds, Fused-Ring
- Therapeutics
- Nucleic Acids, Nucleotides, and Nucleosides
- Hydrocarbons
- Hydrocarbons, Cyclic
- Carbohydrates
- Physical Phenomena
- Alkaloids
- Polycyclic Aromatic Hydrocarbons
- Hydrocarbons, Aromatic
- Polycyclic Compounds
- Glycosides
- Hydrolases
- Enzymes
- Enzymes and Coenzymes
- Indoles
- Purines
- Cytidine
- Pyrimidine Nucleosides
- Pyrimidines
- Pregnadienes
- Pregnanes
- Steroids
- Fused-Ring Compounds
- Steroids, Fluorinated
- Benzene Derivatives
- Sulfonic Acids
- Sulfur Acids
- Phosphoramide Mustards
- Nitrogen Mustard Compounds
- Mustard Compounds
- Hydrocarbons, Halogenated
- Phosphoramides
- Organophosphorus Compounds
- Nucleosides
- Formyltetrahydrofolates
- Tetrahydrofolates
- Folic Acid
- Pterins
- Pteridines
- Pregnadienetriols
- Pregnadienediols
- Amidohydrolases
- Vinca Alkaloids
- Secologanin Tryptamine Alkaloids
- Indole Alkaloids
- Indolizidines
- Indolizines
- Arabinonucleosides
- Aminopterin
- Anthracyclines
- Naphthacenes
- Aminoglycosides
- Coenzymes
- Daunorubicin
- Benzenesulfonates
- Arylsulfonates
- Arylsulfonic Acids
- Sulfhydryl Compounds
- Dexamethasone
- Methotrexate
- Prednisone
- Prednisolone
- Cyclophosphamide
- Cytarabine
- Leucovorin
- Doxorubicin
- Vincristine
- Methylprednisolone
- Asparaginase
- Mercaptopurine
- Thioguanine
- Calcium Dobesilate
- Radiotherapy
- Radiation
- blinatumomab
- dexamethasone 21-phosphate
- deltacortene
- prednylidene
- N,N-dicyclohexyl-isoborneol-10-sulfonamide
- azathiopurine
- merphos
- pegaspargase
- auricularum
- dexamethasone acetate
- asparaginase erwinia chrysanthemi recombinant
Other Study ID Numbers
- NCI-2019-02187 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- U10CA180886 (U.S. NIH Grant/Contract)
- AALL1731 (Other Identifier: CTEP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
NCI is committed to sharing data in accordance with NIH policy.
For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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