Studie zkoumající Blinatumomab v kombinaci s chemoterapií u pacientů s nově diagnostikovanou B-lymfoblastickou leukémií
Studie fáze 3 zkoumající Blinatumomab (NSC# 765986) v kombinaci s chemoterapií u pacientů s nově diagnostikovaným standardním rizikem nebo Downovým syndromem B-lymfoblastická leukémie (B-ALL) a léčba pacientů s lokalizovaným B-lymfoblastickým lymfomem (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.
Přehled studie
Postavení
Intervence / Léčba
- Lék: Cyclophosphamide
- Lék: Doxorubicin Hydrochloride
- Lék: Vincristine Sulfate
- Biologický: Blinatumomab
- Lék: Mercaptopurine
- Lék: Leucovorin Calcium
- Lék: Pegaspargase
- Lék: Dexamethasone
- Lék: Thioguanine
- Lék: Cytarabine
- Lék: Asparaginase Erwinia chrysanthemi
- Lék: Mercaptopurine Oral Suspension
- Lék: Methotrexate
- Lék: Prednisone
- Lék: Prednisolone
- Záření: Radiation Therapy
- Záření: Radiation Therapy
Detailní popis
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.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní místa
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New South Wales
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Hunter Regional Mail Centre, New South Wales, Austrálie, 2310
- John Hunter Children's Hospital
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Westmead, New South Wales, Austrálie, 2145
- The Children's Hospital at Westmead
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Queensland
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South Brisbane, Queensland, Austrálie, 4101
- Queensland Children's Hospital
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South Australia
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North Adelaide, South Australia, Austrálie, 5006
- Women's and Children's Hospital-Adelaide
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Victoria
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Clayton, Victoria, Austrálie, 3168
- Monash Medical Center-Clayton Campus
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Parkville, Victoria, Austrálie, 3052
- Royal Children's Hospital
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Western Australia
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Perth, Western Australia, Austrálie, 6009
- Perth Children's Hospital
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Québec, Kanada, G1V 4G2
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
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Alberta
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Calgary, Alberta, Kanada, T3B 6A8
- Alberta Children's Hospital
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Edmonton, Alberta, Kanada, T6G 2B7
- University of Alberta Hospital
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British Columbia
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Vancouver, British Columbia, Kanada, V6H 3V4
- British Columbia Children's Hospital
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Manitoba
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Winnipeg, Manitoba, Kanada, R3E 0V9
- CancerCare Manitoba
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Newfoundland and Labrador
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St. John's, Newfoundland and Labrador, Kanada, A1B 3V6
- Janeway Child Health Centre
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Nova Scotia
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Halifax, Nova Scotia, Kanada, B3K 6R8
- IWK Health Centre
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Ontario
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Hamilton, Ontario, Kanada, L8N 3Z5
- McMaster Children's Hospital at Hamilton Health Sciences
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Kingston, Ontario, Kanada, K7L 2V7
- Kingston Health Sciences Centre
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London, Ontario, Kanada, N6A 5W9
- Children's Hospital
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Ottawa, Ontario, Kanada, K1H 8L1
- Children's Hospital of Eastern Ontario
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Toronto, Ontario, Kanada, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Kanada, H3H 1P3
- The Montreal Children's Hospital of the MUHC
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Sherbrooke, Quebec, Kanada, J1H 5N4
- Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
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Saskatchewan
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Saskatoon, Saskatchewan, Kanada, S7N 4H4
- Saskatoon Cancer Centre
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Saskatoon, Saskatchewan, Kanada, S7N 0W8
- Jim Pattison Children's Hospital
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Christchurch, Nový Zéland, 8011
- Christchurch Hospital
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Auckland
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Grafton, Auckland, Nový Zéland, 1145
- Starship Children's Hospital
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Caguas, Portoriko, 00726
- HIMA San Pablo Oncologic Hospital
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San Juan, Portoriko, 00926
- University Pediatric Hospital
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Alabama
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Birmingham, Alabama, Spojené státy, 35233
- Children's Hospital of Alabama
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Mobile, Alabama, Spojené státy, 36604
- USA Health Strada Patient Care Center
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Alaska
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Anchorage, Alaska, Spojené státy, 99508
- Providence Alaska Medical Center
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Arizona
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Mesa, Arizona, Spojené státy, 85202
- Banner Children's at Desert
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Phoenix, Arizona, Spojené státy, 85016
- Phoenix Childrens Hospital
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Tucson, Arizona, Spojené státy, 85719
- Banner University Medical Center - Tucson
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Arkansas
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Little Rock, Arkansas, Spojené státy, 72202-3591
- Arkansas Children's Hospital
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California
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Downey, California, Spojené státy, 90242
- Kaiser Permanente Downey Medical Center
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Duarte, California, Spojené státy, 91010
- City of Hope Comprehensive Cancer Center
-
Loma Linda, California, Spojené státy, 92354
- Loma Linda University Medical Center
-
Long Beach, California, Spojené státy, 90806
- Miller Children's and Women's Hospital Long Beach
-
Los Angeles, California, Spojené státy, 90048
- Cedars-Sinai Medical Center
-
Los Angeles, California, Spojené státy, 90027
- Children's Hospital Los Angeles
-
Los Angeles, California, Spojené státy, 90095
- Mattel Children's Hospital UCLA
-
Madera, California, Spojené státy, 93636
- Valley Children's Hospital
-
Oakland, California, Spojené státy, 94609
- UCSF Benioff Children's Hospital Oakland
-
Oakland, California, Spojené státy, 94611
- Kaiser Permanente-Oakland
-
Orange, California, Spojené státy, 92868
- Children's Hospital of Orange County
-
Palo Alto, California, Spojené státy, 94304
- Lucile Packard Children's Hospital Stanford University
-
Sacramento, California, Spojené státy, 95816
- Sutter Medical Center Sacramento
-
Sacramento, California, Spojené státy, 95817
- University of California Davis Comprehensive Cancer Center
-
San Diego, California, Spojené státy, 92123
- Rady Children's Hospital - San Diego
-
San Diego, California, Spojené státy, 92134
- Naval Medical Center -San Diego
-
San Francisco, California, Spojené státy, 94158
- UCSF Medical Center-Mission Bay
-
Santa Barbara, California, Spojené státy, 93102
- Santa Barbara Cottage Hospital
-
Torrance, California, Spojené státy, 90502
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
-
-
Colorado
-
Aurora, Colorado, Spojené státy, 80045
- Children's Hospital Colorado
-
Denver, Colorado, Spojené státy, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
-
-
Connecticut
-
Hartford, Connecticut, Spojené státy, 06106
- Connecticut Children's Medical Center
-
New Haven, Connecticut, Spojené státy, 06520
- Yale University
-
-
Delaware
-
Wilmington, Delaware, Spojené státy, 19803
- Alfred I duPont Hospital for Children
-
-
District of Columbia
-
Washington D.C., District of Columbia, Spojené státy, 20010
- Children's National Medical Center
-
Washington D.C., District of Columbia, Spojené státy, 20007
- MedStar Georgetown University Hospital
-
-
Florida
-
Fort Lauderdale, Florida, Spojené státy, 33316
- Broward Health Medical Center
-
Fort Myers, Florida, Spojené státy, 33908
- Golisano Children's Hospital of Southwest Florida
-
Gainesville, Florida, Spojené státy, 32610
- UF Health Cancer Institute - Gainesville
-
Hollywood, Florida, Spojené státy, 33021
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
-
Jacksonville, Florida, Spojené státy, 32207
- Nemours Children's Clinic-Jacksonville
-
Loxahatchee Groves, Florida, Spojené státy, 33470
- Palms West Radiation Therapy
-
Miami, Florida, Spojené státy, 33155
- Nicklaus Children's Hospital
-
Miami, Florida, Spojené státy, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
-
Miami, Florida, Spojené státy, 33176
- Miami Cancer Institute
-
Orlando, Florida, Spojené státy, 32827
- Nemours Children's Hospital
-
Orlando, Florida, Spojené státy, 32803
- AdventHealth Orlando
-
Orlando, Florida, Spojené státy, 32806
- Arnold Palmer Hospital for Children
-
Pensacola, Florida, Spojené státy, 32504
- Sacred Heart Hospital
-
St. Petersburg, Florida, Spojené státy, 33701
- Johns Hopkins All Children's Hospital
-
Tampa, Florida, Spojené státy, 33606
- Tampa General Hospital
-
Tampa, Florida, Spojené státy, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
-
West Palm Beach, Florida, Spojené státy, 33407
- Saint Mary's Medical Center
-
-
Georgia
-
Atlanta, Georgia, Spojené státy, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
-
Augusta, Georgia, Spojené státy, 30912
- Augusta University Medical Center
-
Macon, Georgia, Spojené státy, 31201
- Atrium Health Navicent
-
Savannah, Georgia, Spojené státy, 31404
- Memorial Health University Medical Center
-
-
Hawaii
-
Honolulu, Hawaii, Spojené státy, 96826
- Kapiolani Medical Center for Women and Children
-
Honolulu, Hawaii, Spojené státy, 96859
- Tripler Army Medical Center
-
-
Idaho
-
Boise, Idaho, Spojené státy, 83712
- Saint Luke's Cancer Institute - Boise
-
-
Illinois
-
Chicago, Illinois, Spojené státy, 60637
- University of Chicago Comprehensive Cancer Center
-
Chicago, Illinois, Spojené státy, 60612
- University of Illinois
-
Chicago, Illinois, Spojené státy, 60611
- Lurie Children's Hospital-Chicago
-
Maywood, Illinois, Spojené státy, 60153
- Loyola University Medical Center
-
Oak Lawn, Illinois, Spojené státy, 60453
- Advocate Children's Hospital-Oak Lawn
-
Park Ridge, Illinois, Spojené státy, 60068
- Advocate Children's Hospital-Park Ridge
-
Peoria, Illinois, Spojené státy, 61637
- OSF Children's Hospital of Illinois
-
Springfield, Illinois, Spojené státy, 62702
- Southern Illinois University School of Medicine
-
Winfield, Illinois, Spojené státy, 60190
- Northwestern Medicine Central DuPage Hospital
-
-
Indiana
-
Indianapolis, Indiana, Spojené státy, 46202
- Riley Hospital for Children
-
Indianapolis, Indiana, Spojené státy, 46260
- Ascension Saint Vincent Indianapolis Hospital
-
-
Iowa
-
Des Moines, Iowa, Spojené státy, 50309
- Blank Children's Hospital
-
Iowa City, Iowa, Spojené státy, 52242
- University of Iowa/Holden Comprehensive Cancer Center
-
-
Kentucky
-
Lexington, Kentucky, Spojené státy, 40536
- University of Kentucky/Markey Cancer Center
-
Louisville, Kentucky, Spojené státy, 40202
- Norton Children's Hospital
-
-
Louisiana
-
New Orleans, Louisiana, Spojené státy, 70121
- Ochsner Medical Center Jefferson
-
New Orleans, Louisiana, Spojené státy, 70118
- Children's Hospital New Orleans
-
-
Maine
-
Bangor, Maine, Spojené státy, 04401
- Eastern Maine Medical Center
-
Scarborough, Maine, Spojené státy, 04074
- Maine Children's Cancer Program
-
-
Maryland
-
Baltimore, Maryland, Spojené státy, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
-
Baltimore, Maryland, Spojené státy, 21215
- Sinai Hospital of Baltimore
-
Baltimore, Maryland, Spojené státy, 21201
- University of Maryland/Greenebaum Cancer Center
-
Bethesda, Maryland, Spojené státy, 20889-5600
- Walter Reed National Military Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, Spojené státy, 02215
- Dana-Farber Cancer Institute
-
Boston, Massachusetts, Spojené státy, 02114
- Massachusetts General Hospital Cancer Center
-
Boston, Massachusetts, Spojené státy, 02111
- Tufts Children's Hospital
-
Springfield, Massachusetts, Spojené státy, 01199
- Baystate Medical Center
-
Worcester, Massachusetts, Spojené státy, 01655
- UMass Memorial Medical Center - University Campus
-
-
Michigan
-
Ann Arbor, Michigan, Spojené státy, 48109
- C S Mott Children's Hospital
-
Detroit, Michigan, Spojené státy, 48201
- Children's Hospital of Michigan
-
Detroit, Michigan, Spojené státy, 48236
- Henry Ford Health Saint John Hospital
-
East Lansing, Michigan, Spojené státy, 48823
- Michigan State University
-
Grand Rapids, Michigan, Spojené státy, 49503
- Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
-
Kalamazoo, Michigan, Spojené státy, 49007
- Bronson Methodist Hospital
-
Royal Oak, Michigan, Spojené státy, 48073
- Corewell Health Children's
-
-
Minnesota
-
Minneapolis, Minnesota, Spojené státy, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
-
Minneapolis, Minnesota, Spojené státy, 55455
- University of Minnesota/Masonic Cancer Center
-
Rochester, Minnesota, Spojené státy, 55905
- Mayo Clinic in Rochester
-
-
Mississippi
-
Jackson, Mississippi, Spojené státy, 39216
- University of Mississippi Medical Center
-
-
Missouri
-
Columbia, Missouri, Spojené státy, 65212
- University of Missouri Children's Hospital
-
Kansas City, Missouri, Spojené státy, 64108
- Children's Mercy Hospitals and Clinics
-
St Louis, Missouri, Spojené státy, 63110
- Washington University School of Medicine
-
St Louis, Missouri, Spojené státy, 63141
- Mercy Hospital Saint Louis
-
St Louis, Missouri, Spojené státy, 63104
- Cardinal Glennon Children's Medical Center
-
-
Nebraska
-
Omaha, Nebraska, Spojené státy, 68198
- University of Nebraska Medical Center
-
Omaha, Nebraska, Spojené státy, 68114
- Children's Hospital and Medical Center of Omaha
-
-
Nevada
-
Las Vegas, Nevada, Spojené státy, 89144
- Summerlin Hospital Medical Center
-
Las Vegas, Nevada, Spojené státy, 89109
- Sunrise Hospital and Medical Center
-
Las Vegas, Nevada, Spojené státy, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
-
Las Vegas, Nevada, Spojené státy, 89102
- University Medical Center of Southern Nevada
-
Reno, Nevada, Spojené státy, 89502
- Renown Regional Medical Center
-
-
New Hampshire
-
Lebanon, New Hampshire, Spojené státy, 03756
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
-
-
New Jersey
-
Hackensack, New Jersey, Spojené státy, 07601
- Hackensack University Medical Center
-
Morristown, New Jersey, Spojené státy, 07960
- Morristown Medical Center
-
Neptune City, New Jersey, Spojené státy, 07753
- Jersey Shore Medical Center
-
New Brunswick, New Jersey, Spojené státy, 08901
- Saint Peter's University Hospital
-
New Brunswick, New Jersey, Spojené státy, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
-
Newark, New Jersey, Spojené státy, 07112
- Newark Beth Israel Medical Center
-
Paterson, New Jersey, Spojené státy, 07503
- Saint Joseph's Regional Medical Center
-
-
New Mexico
-
Albuquerque, New Mexico, Spojené státy, 87106
- Presbyterian Hospital
-
Albuquerque, New Mexico, Spojené státy, 87106
- University of New Mexico Cancer Center
-
-
New York
-
Albany, New York, Spojené státy, 12208
- Albany Medical Center
-
Brooklyn, New York, Spojené státy, 11219
- Maimonides Medical Center
-
Mineola, New York, Spojené státy, 11501
- NYU Langone Hospital - Long Island
-
New Hyde Park, New York, Spojené státy, 11040
- The Steven and Alexandra Cohen Children's Medical Center of New York
-
New York, New York, Spojené státy, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Spojené státy, 10029
- Mount Sinai Hospital
-
New York, New York, Spojené státy, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
-
New York, New York, Spojené státy, 10065
- NYP/Weill Cornell Medical Center
-
New York, New York, Spojené státy, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
-
Rochester, New York, Spojené státy, 14642
- University of Rochester
-
Stony Brook, New York, Spojené státy, 11794
- Stony Brook University Medical Center
-
Syracuse, New York, Spojené státy, 13210
- State University of New York Upstate Medical University
-
The Bronx, New York, Spojené státy, 10467
- Montefiore Medical Center - Moses Campus
-
Valhalla, New York, Spojené státy, 10595
- New York Medical College
-
-
North Carolina
-
Asheville, North Carolina, Spojené státy, 28801
- Mission Hospital
-
Chapel Hill, North Carolina, Spojené státy, 27599
- UNC Lineberger Comprehensive Cancer Center
-
Charlotte, North Carolina, Spojené státy, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Charlotte, North Carolina, Spojené státy, 28204
- Novant Health Presbyterian Medical Center
-
Durham, North Carolina, Spojené státy, 27710
- Duke University Medical Center
-
Greenville, North Carolina, Spojené státy, 27834
- East Carolina University
-
Winston-Salem, North Carolina, Spojené státy, 27157
- Wake Forest University Health Sciences
-
-
North Dakota
-
Fargo, North Dakota, Spojené státy, 58122
- Sanford Broadway Medical Center
-
-
Ohio
-
Akron, Ohio, Spojené státy, 44308
- Children's Hospital Medical Center of Akron
-
Cincinnati, Ohio, Spojené státy, 45229
- Cincinnati Children's Hospital Medical Center
-
Cleveland, Ohio, Spojené státy, 44195
- Cleveland Clinic Foundation
-
Cleveland, Ohio, Spojené státy, 44106
- Rainbow Babies and Childrens Hospital
-
Columbus, Ohio, Spojené státy, 43205
- Nationwide Children's Hospital
-
Dayton, Ohio, Spojené státy, 45404
- Dayton Children's Hospital
-
Toledo, Ohio, Spojené státy, 43606
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
-
-
Oklahoma
-
Oklahoma City, Oklahoma, Spojené státy, 73104
- University of Oklahoma Health Sciences Center
-
Tulsa, Oklahoma, Spojené státy, 74136
- Saint Francis Children's Hospital
-
-
Oregon
-
Portland, Oregon, Spojené státy, 97239
- Oregon Health and Science University
-
Portland, Oregon, Spojené státy, 97227
- Legacy Emanuel Children's Hospital
-
-
Pennsylvania
-
Allentown, Pennsylvania, Spojené státy, 18103
- Lehigh Valley Hospital-Cedar Crest
-
Danville, Pennsylvania, Spojené státy, 17822
- Geisinger Medical Center
-
Hershey, Pennsylvania, Spojené státy, 17033
- Penn State Children's Hospital
-
Philadelphia, Pennsylvania, Spojené státy, 19104
- Children's Hospital of Philadelphia
-
Philadelphia, Pennsylvania, Spojené státy, 19134
- Saint Christopher's Hospital for Children
-
Pittsburgh, Pennsylvania, Spojené státy, 15224
- Children's Hospital of Pittsburgh of UPMC
-
-
Rhode Island
-
Providence, Rhode Island, Spojené státy, 02903
- Rhode Island Hospital
-
-
South Carolina
-
Charleston, South Carolina, Spojené státy, 29425
- Medical University of South Carolina
-
Columbia, South Carolina, Spojené státy, 29203
- Prisma Health Richland Hospital
-
Greenville, South Carolina, Spojené státy, 29605
- BI-LO Charities Children's Cancer Center
-
-
South Dakota
-
Sioux Falls, South Dakota, Spojené státy, 57117-5134
- Sanford USD Medical Center - Sioux Falls
-
-
Tennessee
-
Chattanooga, Tennessee, Spojené státy, 37403
- T C Thompson Children's Hospital
-
Knoxville, Tennessee, Spojené státy, 37916
- East Tennessee Childrens Hospital
-
Nashville, Tennessee, Spojené státy, 37232
- Vanderbilt University/Ingram Cancer Center
-
Nashville, Tennessee, Spojené státy, 37203
- The Children's Hospital at TriStar Centennial
-
-
Texas
-
Amarillo, Texas, Spojené státy, 79106
- Texas Tech University Health Sciences Center-Amarillo
-
Austin, Texas, Spojené státy, 78723
- Dell Children's Medical Center of Central Texas
-
Corpus Christi, Texas, Spojené státy, 78411
- Driscoll Children's Hospital
-
Dallas, Texas, Spojené státy, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
-
Dallas, Texas, Spojené státy, 75230
- Medical City Dallas Hospital
-
El Paso, Texas, Spojené státy, 79905
- El Paso Children's Hospital
-
Fort Worth, Texas, Spojené státy, 76104
- Cook Children's Medical Center
-
Houston, Texas, Spojené státy, 77030
- UT MD Anderson Cancer Center
-
Houston, Texas, Spojené státy, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
-
Lubbock, Texas, Spojené státy, 79410
- Covenant Children's Hospital
-
Lubbock, Texas, Spojené státy, 79415
- UMC Cancer Center / UMC Health System
-
McAllen, Texas, Spojené státy, 78503
- Vannie Cook Children's Clinic
-
San Antonio, Texas, Spojené státy, 78229
- University of Texas Health Science Center at San Antonio
-
San Antonio, Texas, Spojené státy, 78207
- Children's Hospital of San Antonio
-
San Antonio, Texas, Spojené státy, 78229
- Methodist Children's Hospital of South Texas
-
Temple, Texas, Spojené státy, 76508
- Scott and White Memorial Hospital
-
-
Utah
-
Salt Lake City, Utah, Spojené státy, 84113
- Primary Children's Hospital
-
-
Vermont
-
Burlington, Vermont, Spojené státy, 05405
- University of Vermont and State Agricultural College
-
-
Virginia
-
Charlottesville, Virginia, Spojené státy, 22908
- University of Virginia Cancer Center
-
Falls Church, Virginia, Spojené státy, 22042
- Inova Fairfax Hospital
-
Norfolk, Virginia, Spojené státy, 23507
- Children's Hospital of The King's Daughters
-
Portsmouth, Virginia, Spojené státy, 23708-2197
- Naval Medical Center - Portsmouth
-
Richmond, Virginia, Spojené státy, 23298
- VCU Massey Comprehensive Cancer Center
-
Roanoke, Virginia, Spojené státy, 24014
- Carilion Children's
-
-
Washington
-
Seattle, Washington, Spojené státy, 98105
- Seattle Children's Hospital
-
Spokane, Washington, Spojené státy, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
-
Tacoma, Washington, Spojené státy, 98405
- Mary Bridge Children's Hospital and Health Center
-
Tacoma, Washington, Spojené státy, 98431
- Madigan Army Medical Center
-
-
West Virginia
-
Charleston, West Virginia, Spojené státy, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
-
Huntington, West Virginia, Spojené státy, 25701
- Edwards Comprehensive Cancer Center
-
Morgantown, West Virginia, Spojené státy, 26506
- West Virginia University Healthcare
-
-
Wisconsin
-
Green Bay, Wisconsin, Spojené státy, 54301
- Saint Vincent Hospital Cancer Center Green Bay
-
Madison, Wisconsin, Spojené státy, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
-
Marshfield, Wisconsin, Spojené státy, 54449
- Marshfield Medical Center-Marshfield
-
Milwaukee, Wisconsin, Spojené státy, 53226
- Children's Hospital of Wisconsin
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Aktivní komparátor: Arm A (SR-Avg control)
Arm A: See detailed description. |
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given PO
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
|
|
Experimentální: Arm B (SR-Avg experimental)
Arm B: See detailed description. |
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given PO
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
|
|
Aktivní komparátor: Arm C (SR-High Control)
Arm C: See detailed description. |
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given PO
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
|
|
Experimentální: Arm D (SR-High experimental)
Arm D See detailed description. |
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given PO
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
|
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Experimentální: B-LLy
See detailed description. |
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given PO
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO or IV
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Experimentální: DS B-ALL
See detailed description. |
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given PO
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Undergo cranial radiation therapy
Ostatní jména:
Undergo testicular radiation therapy
Ostatní jména:
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Experimentální: NCI SR or HR DS B-ALL
See detailed description. |
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given IV
Ostatní jména:
Given PO
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO or IV
Ostatní jména:
Given IV or IM
Ostatní jména:
Given PO
Ostatní jména:
Given IT or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
Given PO or IV
Ostatní jména:
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
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
Časové okno: 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)
Časové okno: 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
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
To explore adaptive and innate immune functions and host genetic factors associated with severe infectious complications in children with DS B-ALL
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Sumit Gupta, Children's Oncology Group
Publikace a užitečné odkazy
Obecné publikace
- 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.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Další relevantní podmínky MeSH
- Neurologické projevy
- Nemoci nervového systému
- Novotvary
- Genetické choroby, vrozené
- Onemocnění imunitního systému
- Infekce
- Virová onemocnění
- Novotvary podle histologického typu
- Neurobehaviorální projevy
- Hematologická onemocnění
- DNA virové infekce
- Lymfatická onemocnění
- Lymfoproliferativní poruchy
- Imunoproliferativní poruchy
- Lymfom, Non-Hodgkin
- Vrozené vady
- Lymfom, B-buňka
- Lymfom
- Abnormality, vícenásobné
- Intelektuální postižení
- Leukémie, lymfoidní
- Leukémie
- Infekce virem Epstein-Barrové
- Herpesviridae infekce
- Nádorové virové infekce
- Chromozomové poruchy
- Lymfoblastická leukémie-lymfom prekurzorových buněk
- Vrozené, dědičné a neonatální nemoci a abnormality
- Hemická a lymfatická onemocnění
- Burkittův lymfom
- Downův syndrom
- Prekurzorová B-buněčná lymfoblastická leukémie-lymfom
- Sloučeniny síry
- Organické chemikálie
- Heterocyklické sloučeniny, 1 kruh
- Heterocyklické sloučeniny
- Heterocyklické sloučeniny, 2-prsten
- Heterocyklické sloučeniny, fúzované kroužek
- Terapeutika
- Nukleové kyseliny, nukleotidy a nukleosidy
- Uhlovodíky
- Uhlovodíky, cyklické
- Uhlohydráty
- Fyzické jevy
- Alkaloidy
- Polycyklické aromatické uhlovodíky
- Uhlovodíky, aromatické
- Polycyklické sloučeniny
- Glykosidy
- Hydrolázy
- Enzymy
- Enzymy a koenzymy
- Indoly
- Puriny
- Cytidin
- Pyrimidinové nukleosidy
- Pyrimidiny
- Těhotenství
- Těhotenství
- Steroidy
- Sloučeniny roztaveného kruhu
- Steroidy, fluorované
- Deriváty benzenu
- Kyseliny sulfonové
- Kyseliny síry
- Fosforamidové hořčice
- Sloučeniny hořčice dusíku
- Hořčičné sloučeniny
- Uhlovodíky, halogenované
- Fosforamidy
- Organofosforové sloučeniny
- Nukleosidy
- Formyltetrahydrofoláty
- Tetrahydrofoláty
- Kyselina listová
- Pteriny
- Pteridiny
- Těhotenství
- Těhotenství
- Amidohydrolázy
- Vinca alkaloidy
- Alkaloidy tryptaminu sezologaninu
- Indolské alkaloidy
- Indolizidiny
- Indoliziny
- Arabinonukleosidy
- Aminopterin
- Antracykliny
- Nafthacenes
- Aminoglykosidy
- Koenzymy
- Daunorubicin
- Benzenesulfonáty
- Arylsulfonáty
- Kyseliny arylsulfonové
- Sloučeniny sulfhydrylu
- Dexamethason
- Methotrexát
- Prednison
- Prednisolon
- Cyklofosfamid
- Cytarabin
- Leukovorin
- Doxorubicin
- Vinkristine
- Methylprednisolon
- Asparagináza
- Merkaptopurin
- Thioguanin
- Dobesilát vápenatý
- Radioterapie
- Záření
- BLINATUMOMAB
- Dexamethason 21-fosfát
- deltacortene
- prednyliden
- N, N-dicyklohexyl-isoborneol-10-sulfonamid
- azathiopurin
- Merphos
- pegaspargase
- Auricularum
- dexamethason acetát
- asparagináza erwinia chrysanthemi rekombinantní
Další identifikační čísla studie
- NCI-2019-02187
- U10CA180886 (Grant/smlouva NIH USA)
- NCI-2019-02187 (Identifikátor registru: CTRP (Clinical Trial Reporting Program))
- AALL1731 (Jiný identifikátor: CTEP)
- AALL1731 (Jiný identifikátor: Children's Oncology Group)
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