새로 진단된 B-림프구성 백혈병 환자에서 화학요법과 병용한 Blinatumomab을 조사하기 위한 연구
새로 진단된 표준 위험 또는 다운 증후군 B-림프구성 백혈병(B-ALL) 환자의 화학요법과 병용 블리나투모맙(NSC# 765986) 및 국소 B-림프구성 림프종(B-LLy) 환자의 치료를 조사하는 3상 시험
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.
연구 개요
상태
개입 / 치료
- 의약품: Cyclophosphamide
- 의약품: Doxorubicin Hydrochloride
- 의약품: Vincristine Sulfate
- 생물학적: Blinatumomab
- 의약품: Mercaptopurine
- 의약품: Leucovorin Calcium
- 의약품: Pegaspargase
- 의약품: Dexamethasone
- 의약품: Thioguanine
- 의약품: Cytarabine
- 의약품: Asparaginase Erwinia chrysanthemi
- 의약품: Mercaptopurine Oral Suspension
- 의약품: Methotrexate
- 의약품: Prednisone
- 의약품: Prednisolone
- 방사능: Radiation Therapy
- 방사능: Radiation Therapy
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 3단계
연락처 및 위치
연구 장소
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Christchurch, 뉴질랜드, 8011
- Christchurch Hospital
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Auckland
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Grafton, Auckland, 뉴질랜드, 1145
- Starship Children's Hospital
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Alabama
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Birmingham, Alabama, 미국, 35233
- Children's Hospital of Alabama
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Mobile, Alabama, 미국, 36604
- USA Health Strada Patient Care Center
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Alaska
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Anchorage, Alaska, 미국, 99508
- Providence Alaska Medical Center
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Arizona
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Mesa, Arizona, 미국, 85202
- Banner Children's at Desert
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Phoenix, Arizona, 미국, 85016
- Phoenix Childrens Hospital
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Tucson, Arizona, 미국, 85719
- Banner University Medical Center - Tucson
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Arkansas
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Little Rock, Arkansas, 미국, 72202-3591
- Arkansas Children's Hospital
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California
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Downey, California, 미국, 90242
- Kaiser Permanente Downey Medical Center
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Duarte, California, 미국, 91010
- City of Hope Comprehensive Cancer Center
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Loma Linda, California, 미국, 92354
- Loma Linda University Medical Center
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Long Beach, California, 미국, 90806
- Miller Children's and Women's Hospital Long Beach
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Los Angeles, California, 미국, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, 미국, 90027
- Children's Hospital Los Angeles
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Los Angeles, California, 미국, 90095
- Mattel Children's Hospital UCLA
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Madera, California, 미국, 93636
- Valley Children's Hospital
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Oakland, California, 미국, 94609
- UCSF Benioff Children's Hospital Oakland
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Oakland, California, 미국, 94611
- Kaiser Permanente-Oakland
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Orange, California, 미국, 92868
- Children's Hospital of Orange County
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Palo Alto, California, 미국, 94304
- Lucile Packard Children's Hospital Stanford University
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Sacramento, California, 미국, 95816
- Sutter Medical Center Sacramento
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Sacramento, California, 미국, 95817
- University of California Davis Comprehensive Cancer Center
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San Diego, California, 미국, 92123
- Rady Children's Hospital - San Diego
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San Diego, California, 미국, 92134
- Naval Medical Center -San Diego
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San Francisco, California, 미국, 94158
- UCSF Medical Center-Mission Bay
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Santa Barbara, California, 미국, 93102
- Santa Barbara Cottage Hospital
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Torrance, California, 미국, 90502
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
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Colorado
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Aurora, Colorado, 미국, 80045
- Children's Hospital Colorado
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Denver, Colorado, 미국, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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Connecticut
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Hartford, Connecticut, 미국, 06106
- Connecticut Children's Medical Center
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New Haven, Connecticut, 미국, 06520
- Yale University
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Delaware
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Wilmington, Delaware, 미국, 19803
- Alfred I duPont Hospital for Children
-
-
District of Columbia
-
Washington D.C., District of Columbia, 미국, 20010
- Children's National Medical Center
-
Washington D.C., District of Columbia, 미국, 20007
- MedStar Georgetown University Hospital
-
-
Florida
-
Fort Lauderdale, Florida, 미국, 33316
- Broward Health Medical Center
-
Fort Myers, Florida, 미국, 33908
- Golisano Children's Hospital of Southwest Florida
-
Gainesville, Florida, 미국, 32610
- UF Health Cancer Institute - Gainesville
-
Hollywood, Florida, 미국, 33021
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
-
Jacksonville, Florida, 미국, 32207
- Nemours Children's Clinic-Jacksonville
-
Loxahatchee Groves, Florida, 미국, 33470
- Palms West Radiation Therapy
-
Miami, Florida, 미국, 33155
- Nicklaus Children's Hospital
-
Miami, Florida, 미국, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
-
Miami, Florida, 미국, 33176
- Miami Cancer Institute
-
Orlando, Florida, 미국, 32827
- Nemours Children's Hospital
-
Orlando, Florida, 미국, 32803
- AdventHealth Orlando
-
Orlando, Florida, 미국, 32806
- Arnold Palmer Hospital for Children
-
Pensacola, Florida, 미국, 32504
- Sacred Heart Hospital
-
St. Petersburg, Florida, 미국, 33701
- Johns Hopkins All Children's Hospital
-
Tampa, Florida, 미국, 33606
- Tampa General Hospital
-
Tampa, Florida, 미국, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
-
West Palm Beach, Florida, 미국, 33407
- Saint Mary's Medical Center
-
-
Georgia
-
Atlanta, Georgia, 미국, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
-
Augusta, Georgia, 미국, 30912
- Augusta University Medical Center
-
Macon, Georgia, 미국, 31201
- Atrium Health Navicent
-
Savannah, Georgia, 미국, 31404
- Memorial Health University Medical Center
-
-
Hawaii
-
Honolulu, Hawaii, 미국, 96826
- Kapiolani Medical Center for Women and Children
-
Honolulu, Hawaii, 미국, 96859
- Tripler Army Medical Center
-
-
Idaho
-
Boise, Idaho, 미국, 83712
- Saint Luke's Cancer Institute - Boise
-
-
Illinois
-
Chicago, Illinois, 미국, 60637
- University of Chicago Comprehensive Cancer Center
-
Chicago, Illinois, 미국, 60612
- University of Illinois
-
Chicago, Illinois, 미국, 60611
- Lurie Children's Hospital-Chicago
-
Maywood, Illinois, 미국, 60153
- Loyola University Medical Center
-
Oak Lawn, Illinois, 미국, 60453
- Advocate Children's Hospital-Oak Lawn
-
Park Ridge, Illinois, 미국, 60068
- Advocate Children's Hospital-Park Ridge
-
Peoria, Illinois, 미국, 61637
- OSF Children's Hospital of Illinois
-
Springfield, Illinois, 미국, 62702
- Southern Illinois University School of Medicine
-
Winfield, Illinois, 미국, 60190
- Northwestern Medicine Central DuPage Hospital
-
-
Indiana
-
Indianapolis, Indiana, 미국, 46202
- Riley Hospital for Children
-
Indianapolis, Indiana, 미국, 46260
- Ascension Saint Vincent Indianapolis Hospital
-
-
Iowa
-
Des Moines, Iowa, 미국, 50309
- Blank Children's Hospital
-
Iowa City, Iowa, 미국, 52242
- University of Iowa/Holden Comprehensive Cancer Center
-
-
Kentucky
-
Lexington, Kentucky, 미국, 40536
- University of Kentucky/Markey Cancer Center
-
Louisville, Kentucky, 미국, 40202
- Norton Children's Hospital
-
-
Louisiana
-
New Orleans, Louisiana, 미국, 70121
- Ochsner Medical Center Jefferson
-
New Orleans, Louisiana, 미국, 70118
- Children's Hospital New Orleans
-
-
Maine
-
Bangor, Maine, 미국, 04401
- Eastern Maine Medical Center
-
Scarborough, Maine, 미국, 04074
- Maine Children's Cancer Program
-
-
Maryland
-
Baltimore, Maryland, 미국, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
Baltimore, Maryland, 미국, 21215
- Sinai Hospital of Baltimore
-
Baltimore, Maryland, 미국, 21201
- University of Maryland/Greenebaum Cancer Center
-
Bethesda, Maryland, 미국, 20889-5600
- Walter Reed National Military Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, 미국, 02215
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital Cancer Center
-
Boston, Massachusetts, 미국, 02111
- Tufts Children's Hospital
-
Springfield, Massachusetts, 미국, 01199
- Baystate Medical Center
-
Worcester, Massachusetts, 미국, 01655
- UMass Memorial Medical Center - University Campus
-
-
Michigan
-
Ann Arbor, Michigan, 미국, 48109
- C S Mott Children's Hospital
-
Detroit, Michigan, 미국, 48201
- Children's Hospital of Michigan
-
Detroit, Michigan, 미국, 48236
- Henry Ford Health Saint John Hospital
-
East Lansing, Michigan, 미국, 48823
- Michigan State University
-
Grand Rapids, Michigan, 미국, 49503
- Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
-
Kalamazoo, Michigan, 미국, 49007
- Bronson Methodist Hospital
-
Royal Oak, Michigan, 미국, 48073
- Corewell Health Children's
-
-
Minnesota
-
Minneapolis, Minnesota, 미국, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
-
Minneapolis, Minnesota, 미국, 55455
- University of Minnesota/Masonic Cancer Center
-
Rochester, Minnesota, 미국, 55905
- Mayo Clinic in Rochester
-
-
Mississippi
-
Jackson, Mississippi, 미국, 39216
- University of Mississippi Medical Center
-
-
Missouri
-
Columbia, Missouri, 미국, 65212
- University of Missouri Children's Hospital
-
Kansas City, Missouri, 미국, 64108
- Children's Mercy Hospitals and Clinics
-
St Louis, Missouri, 미국, 63110
- Washington University School of Medicine
-
St Louis, Missouri, 미국, 63141
- Mercy Hospital Saint Louis
-
St Louis, Missouri, 미국, 63104
- Cardinal Glennon Children's Medical Center
-
-
Nebraska
-
Omaha, Nebraska, 미국, 68198
- University of Nebraska Medical Center
-
Omaha, Nebraska, 미국, 68114
- Children's Hospital and Medical Center of Omaha
-
-
Nevada
-
Las Vegas, Nevada, 미국, 89144
- Summerlin Hospital Medical Center
-
Las Vegas, Nevada, 미국, 89109
- Sunrise Hospital and Medical Center
-
Las Vegas, Nevada, 미국, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
-
Las Vegas, Nevada, 미국, 89102
- University Medical Center of Southern Nevada
-
Reno, Nevada, 미국, 89502
- Renown Regional Medical Center
-
-
New Hampshire
-
Lebanon, New Hampshire, 미국, 03756
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
-
-
New Jersey
-
Hackensack, New Jersey, 미국, 07601
- Hackensack University Medical Center
-
Morristown, New Jersey, 미국, 07960
- Morristown Medical Center
-
Neptune City, New Jersey, 미국, 07753
- Jersey Shore Medical Center
-
New Brunswick, New Jersey, 미국, 08901
- Saint Peter's University Hospital
-
New Brunswick, New Jersey, 미국, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
-
Newark, New Jersey, 미국, 07112
- Newark Beth Israel Medical Center
-
Paterson, New Jersey, 미국, 07503
- Saint Joseph's Regional Medical Center
-
-
New Mexico
-
Albuquerque, New Mexico, 미국, 87106
- Presbyterian Hospital
-
Albuquerque, New Mexico, 미국, 87106
- University of New Mexico Cancer Center
-
-
New York
-
Albany, New York, 미국, 12208
- Albany Medical Center
-
Brooklyn, New York, 미국, 11219
- Maimonides Medical Center
-
Mineola, New York, 미국, 11501
- NYU Langone Hospital - Long Island
-
New Hyde Park, New York, 미국, 11040
- The Steven and Alexandra Cohen Children's Medical Center of New York
-
New York, New York, 미국, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, 미국, 10029
- Mount Sinai Hospital
-
New York, New York, 미국, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, 미국, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, 미국, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Rochester, New York, 미국, 14642
- University of Rochester
-
Stony Brook, New York, 미국, 11794
- Stony Brook University Medical Center
-
Syracuse, New York, 미국, 13210
- State University of New York Upstate Medical University
-
The Bronx, New York, 미국, 10467
- Montefiore Medical Center - Moses Campus
-
Valhalla, New York, 미국, 10595
- New York Medical College
-
-
North Carolina
-
Asheville, North Carolina, 미국, 28801
- Mission Hospital
-
Chapel Hill, North Carolina, 미국, 27599
- UNC Lineberger Comprehensive Cancer Center
-
Charlotte, North Carolina, 미국, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Charlotte, North Carolina, 미국, 28204
- Novant Health Presbyterian Medical Center
-
Durham, North Carolina, 미국, 27710
- Duke University Medical Center
-
Greenville, North Carolina, 미국, 27834
- East Carolina University
-
Winston-Salem, North Carolina, 미국, 27157
- Wake Forest University Health Sciences
-
-
North Dakota
-
Fargo, North Dakota, 미국, 58122
- Sanford Broadway Medical Center
-
-
Ohio
-
Akron, Ohio, 미국, 44308
- Children's Hospital Medical Center of Akron
-
Cincinnati, Ohio, 미국, 45229
- Cincinnati Children's Hospital Medical Center
-
Cleveland, Ohio, 미국, 44195
- Cleveland Clinic Foundation
-
Cleveland, Ohio, 미국, 44106
- Rainbow Babies and Childrens Hospital
-
Columbus, Ohio, 미국, 43205
- Nationwide Children's Hospital
-
Dayton, Ohio, 미국, 45404
- Dayton Children's Hospital
-
Toledo, Ohio, 미국, 43606
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
-
-
Oklahoma
-
Oklahoma City, Oklahoma, 미국, 73104
- University of Oklahoma Health Sciences Center
-
Tulsa, Oklahoma, 미국, 74136
- Saint Francis Children's Hospital
-
-
Oregon
-
Portland, Oregon, 미국, 97239
- Oregon Health and Science University
-
Portland, Oregon, 미국, 97227
- Legacy Emanuel Children's Hospital
-
-
Pennsylvania
-
Allentown, Pennsylvania, 미국, 18103
- Lehigh Valley Hospital-Cedar Crest
-
Danville, Pennsylvania, 미국, 17822
- Geisinger Medical Center
-
Hershey, Pennsylvania, 미국, 17033
- Penn State Children's Hospital
-
Philadelphia, Pennsylvania, 미국, 19104
- Children's Hospital of Philadelphia
-
Philadelphia, Pennsylvania, 미국, 19134
- Saint Christopher's Hospital for Children
-
Pittsburgh, Pennsylvania, 미국, 15224
- Children's Hospital of Pittsburgh of UPMC
-
-
Rhode Island
-
Providence, Rhode Island, 미국, 02903
- Rhode Island Hospital
-
-
South Carolina
-
Charleston, South Carolina, 미국, 29425
- Medical University of South Carolina
-
Columbia, South Carolina, 미국, 29203
- Prisma Health Richland Hospital
-
Greenville, South Carolina, 미국, 29605
- BI-LO Charities Children's Cancer Center
-
-
South Dakota
-
Sioux Falls, South Dakota, 미국, 57117-5134
- Sanford USD Medical Center - Sioux Falls
-
-
Tennessee
-
Chattanooga, Tennessee, 미국, 37403
- T C Thompson Children's Hospital
-
Knoxville, Tennessee, 미국, 37916
- East Tennessee Childrens Hospital
-
Nashville, Tennessee, 미국, 37232
- Vanderbilt University/Ingram Cancer Center
-
Nashville, Tennessee, 미국, 37203
- The Children's Hospital at TriStar Centennial
-
-
Texas
-
Amarillo, Texas, 미국, 79106
- Texas Tech University Health Sciences Center-Amarillo
-
Austin, Texas, 미국, 78723
- Dell Children's Medical Center of Central Texas
-
Corpus Christi, Texas, 미국, 78411
- Driscoll Children's Hospital
-
Dallas, Texas, 미국, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Dallas, Texas, 미국, 75230
- Medical City Dallas Hospital
-
El Paso, Texas, 미국, 79905
- El Paso Children's Hospital
-
Fort Worth, Texas, 미국, 76104
- Cook Children's Medical Center
-
Houston, Texas, 미국, 77030
- UT MD Anderson Cancer Center
-
Houston, Texas, 미국, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
-
Lubbock, Texas, 미국, 79410
- Covenant Children's Hospital
-
Lubbock, Texas, 미국, 79415
- UMC Cancer Center / UMC Health System
-
McAllen, Texas, 미국, 78503
- Vannie Cook Children's Clinic
-
San Antonio, Texas, 미국, 78229
- University of Texas Health Science Center at San Antonio
-
San Antonio, Texas, 미국, 78207
- Children's Hospital of San Antonio
-
San Antonio, Texas, 미국, 78229
- Methodist Children's Hospital of South Texas
-
Temple, Texas, 미국, 76508
- Scott and White Memorial Hospital
-
-
Utah
-
Salt Lake City, Utah, 미국, 84113
- Primary Children's Hospital
-
-
Vermont
-
Burlington, Vermont, 미국, 05405
- University of Vermont and State Agricultural College
-
-
Virginia
-
Charlottesville, Virginia, 미국, 22908
- University of Virginia Cancer Center
-
Falls Church, Virginia, 미국, 22042
- Inova Fairfax Hospital
-
Norfolk, Virginia, 미국, 23507
- Children's Hospital of The King's Daughters
-
Portsmouth, Virginia, 미국, 23708-2197
- Naval Medical Center - Portsmouth
-
Richmond, Virginia, 미국, 23298
- VCU Massey Comprehensive Cancer Center
-
Roanoke, Virginia, 미국, 24014
- Carilion Children's
-
-
Washington
-
Seattle, Washington, 미국, 98105
- Seattle Children's Hospital
-
Spokane, Washington, 미국, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
-
Tacoma, Washington, 미국, 98405
- Mary Bridge Children's Hospital and Health Center
-
Tacoma, Washington, 미국, 98431
- Madigan Army Medical Center
-
-
West Virginia
-
Charleston, West Virginia, 미국, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
-
Huntington, West Virginia, 미국, 25701
- Edwards Comprehensive Cancer Center
-
Morgantown, West Virginia, 미국, 26506
- West Virginia University Healthcare
-
-
Wisconsin
-
Green Bay, Wisconsin, 미국, 54301
- Saint Vincent Hospital Cancer Center Green Bay
-
Madison, Wisconsin, 미국, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
-
Marshfield, Wisconsin, 미국, 54449
- Marshfield Medical Center-Marshfield
-
Milwaukee, Wisconsin, 미국, 53226
- Children's Hospital of Wisconsin
-
-
-
-
-
Québec, 캐나다, G1V 4G2
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
-
-
Alberta
-
Calgary, Alberta, 캐나다, T3B 6A8
- Alberta Children's Hospital
-
Edmonton, Alberta, 캐나다, T6G 2B7
- University of Alberta Hospital
-
-
British Columbia
-
Vancouver, British Columbia, 캐나다, V6H 3V4
- British Columbia Children's Hospital
-
-
Manitoba
-
Winnipeg, Manitoba, 캐나다, R3E 0V9
- CancerCare Manitoba
-
-
Newfoundland and Labrador
-
St. John's, Newfoundland and Labrador, 캐나다, A1B 3V6
- Janeway Child Health Centre
-
-
Nova Scotia
-
Halifax, Nova Scotia, 캐나다, B3K 6R8
- IWK Health Centre
-
-
Ontario
-
Hamilton, Ontario, 캐나다, L8N 3Z5
- McMaster Children's Hospital at Hamilton Health Sciences
-
Kingston, Ontario, 캐나다, K7L 2V7
- Kingston Health Sciences Centre
-
London, Ontario, 캐나다, N6A 5W9
- Children's Hospital
-
Ottawa, Ontario, 캐나다, K1H 8L1
- Children's Hospital of Eastern Ontario
-
Toronto, Ontario, 캐나다, M5G 1X8
- Hospital for Sick Children
-
-
Quebec
-
Montreal, Quebec, 캐나다, H3H 1P3
- The Montreal Children's Hospital of the MUHC
-
Sherbrooke, Quebec, 캐나다, J1H 5N4
- Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
-
-
Saskatchewan
-
Saskatoon, Saskatchewan, 캐나다, S7N 4H4
- Saskatoon Cancer Centre
-
Saskatoon, Saskatchewan, 캐나다, S7N 0W8
- Jim Pattison Children's Hospital
-
-
-
-
-
Caguas, 푸에르토 리코, 00726
- HIMA San Pablo Oncologic Hospital
-
San Juan, 푸에르토 리코, 00926
- University Pediatric Hospital
-
-
-
-
New South Wales
-
Hunter Regional Mail Centre, New South Wales, 호주, 2310
- John Hunter Children's Hospital
-
Westmead, New South Wales, 호주, 2145
- The Children's Hospital at Westmead
-
-
Queensland
-
South Brisbane, Queensland, 호주, 4101
- Queensland Children's Hospital
-
-
South Australia
-
North Adelaide, South Australia, 호주, 5006
- Women's and Children's Hospital-Adelaide
-
-
Victoria
-
Clayton, Victoria, 호주, 3168
- Monash Medical Center-Clayton Campus
-
Parkville, Victoria, 호주, 3052
- Royal Children's Hospital
-
-
Western Australia
-
Perth, Western Australia, 호주, 6009
- Perth Children's Hospital
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
활성 비교기: Arm A (SR-Avg control)
Arm A: See detailed description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO or IV
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given PO or IV
다른 이름들:
|
|
실험적: Arm B (SR-Avg experimental)
Arm B: See detailed description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO or IV
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
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활성 비교기: Arm C (SR-High Control)
Arm C: See detailed description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO or IV
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given PO or IV
다른 이름들:
Given PO or IV
다른 이름들:
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실험적: Arm D (SR-High experimental)
Arm D See detailed description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO or IV
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given PO or IV
다른 이름들:
Given PO or IV
다른 이름들:
|
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실험적: B-LLy
See detailed description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO or IV
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given PO or IV
다른 이름들:
Given PO or IV
다른 이름들:
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|
실험적: DS B-ALL
See detailed description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO or IV
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Undergo cranial radiation therapy
다른 이름들:
Undergo testicular radiation therapy
다른 이름들:
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실험적: NCI SR or HR DS B-ALL
See detailed description. |
Given IV
다른 이름들:
Given IV
다른 이름들:
Given IV
다른 이름들:
Given PO
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO or IV
다른 이름들:
Given IV or IM
다른 이름들:
Given PO
다른 이름들:
Given IT or IV
다른 이름들:
Given PO or IV
다른 이름들:
Given PO or IV
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
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
기간: 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)
기간: 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
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
To explore adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Sumit Gupta, Children's Oncology Group
간행물 및 유용한 링크
일반 간행물
- 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.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 신경학적 징후
- 신경계 질환
- 신생물
- 유전병, 선천적
- 면역계 질환
- 감염
- 바이러스 질환
- 조직학적 유형에 따른 신생물
- 신경 행동 징후
- 혈액 질환
- DNA 바이러스 감염
- 림프계 질환
- 림프 증식 장애
- 면역증식성 장애
- 림프종, 비호지킨
- 선천적 이상
- 림프종, B세포
- 림프종
- 이상, 다중
- 지적 장애
- 백혈병, 림프
- 백혈병
- 엡스타인-바 바이러스 감염
- 헤르페스바이러스과 감염
- 종양 바이러스 감염
- 염색체 장애
- 전구 세포 림프구성 백혈병-림프종
- 선천성, 유전성, 신생아 질환 및 이상
- 헴 및 림프병
- 버킷 림프종
- 다운 증후군
- 전구체 B세포 림프구성 백혈병-림프종
- 황 화합물
- 유기 화학 물질
- 이종 사이 클릭 화합물, 1- 링
- 이종 사이 클릭 화합물
- 이종 사이 클릭 화합물, 2- 링
- 이종 사이 클릭 화합물, 융합 링
- 치료학
- 핵산, 뉴클레오티드 및 뉴 클레오 시드
- 탄화수소
- 탄화수소, 순환
- 탄수화물
- 물리적 현상
- 알칼로이드
- 다 환식 방향족 탄화수소
- 탄화수소, 방향족
- 다 환식 화합물
- 글리코 사이드
- 가수 분해 효소
- 효소
- 효소 및 코엔자임
- 인돌
- 퓨린
- 시티 딘
- 피리 미딘 뉴 클레오 시드
- 피리 미딘
- Pretadienes
- 임신
- 스테로이드
- 융합 링 화합물
- 스테로이드, 불소
- 벤젠 유도체
- 설 폰산
- 황산
- 포스 포 아미드 머스타드
- 질소 머스타드 화합물
- 겨자 화합물
- 탄화수소, 할로겐화
- 포스 포 아미드
- 유기 인 화합물
- 뉴 클레오 시드
- Formyltetrahydrofolates
- 테트라 하이드로 폴 레이트
- 엽산
- Pterins
- Teridines
- Pregnadienetriols
- Pregnadienediols
- 아미도 하이드로 라제
- Vinca 알칼로이드
- Secologanin Tryptamine 알칼로이드
- 인돌 알칼로이드
- 인돌리 지딘
- 인도인
- 아라비노 뉴 클레오 시드
- 아미노 테린
- 안트라 사이클린
- 나프 타센
- 아미노 글리코 시드
- 코엔자임
- Daunorubicin
- 벤젠 설포 네이트
- 아릴 설포 네이트
- 아릴 설 폰산
- 설페이드릴 화합물
- 덱사메타손
- 메토트렉세이트
- 프레드니손
- 프레드니솔론
- 시클로포스파미드
- 시타라빈
- 류코보린
- 독소루비신
- 빈크리스틴
- 메틸프레드니솔론
- 아스파라기나제
- 메르캅토퓨린
- 티오구아닌
- 칼슘 도베실레이트
- 방사선 요법
- 방사
- 블리나투모 맙
- 덱사메타손 21- 포스페이트
- Deltacortene
- 프레드 닐리 덴
- N, N-Dicyclohexyl-Isoborneol-10-Sulfonamide
- 아자 티오 푸린
- 메르 포스
- 페가 스파 제
- 장막
- 덱사메타손 아세테이트
- 아스파라기나 제 Erwinia Chrysanthemi 재조합
기타 연구 ID 번호
- NCI-2019-02187
- U10CA180886 (미국 NIH 보조금/계약)
- NCI-2019-02187 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- AALL1731 (기타 식별자: CTEP)
- AALL1731 (기타 식별자: Children's Oncology Group)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
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
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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