Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
- Conditions
- B Acute Lymphoblastic LeukemiaAcute Lymphoblastic LeukemiaMixed Phenotype Acute LeukemiaT Acute Lymphoblastic Leukemia
- Interventions
- Procedure: Allogeneic Hematopoietic Stem Cell TransplantationOther: Laboratory Biomarker AnalysisOther: Questionnaire Administration
- Registration Number
- NCT03007147
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
This randomized phase III trial studies how well imatinib mesylate works in combination with two different chemotherapy regimens in treating patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (ALL). Imatinib mesylate has been shown to improve outcomes in children and adolescents with Philadelphia chromosome positive (Ph+) ALL when given with strong chemotherapy, but the combination has many side effects. This trial is testing whether a different chemotherapy regimen may work as well as the stronger one but have fewer side effects when given with imatinib. The trial is also testing how well the combination of chemotherapy and imatinib works in another group of patients with a type of ALL that is similar to Ph+ ALL. This type of ALL is called "ABL-class fusion positive ALL", and because it is similar to Ph+ ALL, is thought it will respond well to the combination of agents used to treat Ph+ ALL.
- Detailed Description
PRIMARY OBJECTIVE:
I. To compare disease-free survival (DFS) of standard risk (SR) pediatric Philadelphia chromosome (Ph)+ acute lymphoblastic leukemia (ALL) treated with continuous imatinib mesylate (imatinib) combined with either a high-risk Children's Oncology Group (COG) ALL chemotherapy backbone or the more intensive European (Es)PhALL chemotherapy backbone.
SECONDARY OBJECTIVES:
I. To compare DFS of SR pediatric Ph+ and ABL-class fusion positive ALL patients treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.
II. To determine the feasibility of administration of imatinib after allogeneic hematopoietic stem cell transplantation (HSCT) in high risk (HR) Ph+ ALL patients.
III. To determine event-free survival (EFS) of HR pediatric Ph+ ALL patients treated with EsPhALL chemotherapy, HSCT in first complete remission and post-HSCT imatinib.
IV. To compare rates of grade 3 or higher infections in standard risk (SR) Ph+ ALL patients between the two randomized arms.
V. To evaluate EFS and overall survival (OS) of all eligible Ph+ALL patients enrolled on the study.
VI. To evaluate OS in SR Ph+ ALL patients. VII. To evaluate OS in HR Ph+ ALL patients. VIII. To evaluate EFS and OS of all eligible ABL-class fusion positive ALL patients enrolled on the study.
EXPLORATORY OBJECTIVES:
I. To describe the toxicities associated with post-HSCT administration of imatinib in HR Ph+ALL patients.
II. To evaluate the long-term toxicities in SR Ph+ ALL patients treated with chemotherapy plus imatinib (no transplant), overall and between both randomized arms.
III. To determine prognostic significance of minimal residual disease (MRD) in Ph+ ALL at various time points during therapy.
IIIa. To evaluate MRD in HR patients just prior to HSCT and then at regular intervals post-HSCT and explore the association of these measurements with long-term outcome.
IIIb. To evaluate concordance of MRD assessments made by IGH-T cell receptor (TCR) polymerase chain reaction (PCR) assay and next generation sequencing (NGS) assays.
IV. To determine and validate if IKZF1 deletions alone (IKZF1del) or with other transcription factor deletions (ie, IKZF1 plus subtype \[IKZF1plus\]) or other identified genetic lesions predict poor outcomes in Ph+/ABL-class Ph-like ALL in patients treated on AALL1631.
V. To determine the frequency and prognostic significance of p190 and p210 BCR::ABL1 fusion variants in pediatric Ph+ ALL/ABL-class Ph-like ALL.
VI. To measure adherence to oral chemotherapeutic agents (imatinib, 6-mercaptopurine and methotrexate) during the maintenance phase in SR Ph+ ALL patients.
VIa. To identify factors associated with poor adherence. VIb. To determine association between relapse risk and adherence to each oral chemotherapeutic agent (separately and combined).
VII. To measure adherence to imatinib after allogeneic HSCT in HR Ph+ ALL patients and identify factors associated with poor adherence.
VIII. To compare DFS of SR ABL-class fusion positive ALL patients treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.
IX. To determine the potential therapeutic impact of major secondary events via pharmacologic inhibitor screens in existing/engineered cell models of Ph+ and ABL-class Ph-like ALL harboring secondary events and to test the in vivo activity of the most compelling candidate compounds from pilot studies using patient-derived xenograft (PDX) models established from Ph+ and ABL-class Ph-like ALL samples collected from patients treated on AALL1631.
X. To decipher the molecular and cellular heterogeneity of chronic myelogenous leukemia (CML)-like versus typical Ph+ ALL via single-cell genomics and functional assays and investigate CML-like phenotypes via single-cell ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) sequencing to identify distinct transcriptomic and mutational profiles that will provide novel opportunities for diagnostic and therapeutic interventions.
OUTLINE:
INDUCTION IA PART 1: Patients receive induction IA according to standard of care on days 1-14.
INDUCTION IA PART 2: Patients receive imatinib mesylate orally (PO) once daily (QD) or twice daily (BID) on days 15-33, prednisolone PO twice daily (BID) or methylprednisolone intravenously (IV) on days 15-28, vincristine sulfate IV over 1 minute on days 15 and 22, daunorubicin hydrochloride IV over 1-15 minutes on days 15 and 22, and methotrexate intrathecally (IT) on day 29.
INDUCTION IB: Patients receive imatinib mesylate PO QD or BID on days 1-35, cyclophosphamide IV over 30-60 minutes on days 1 and 28, mercaptopurine PO on days 1-28, cytarabine IV or subcutaneously (SC) on days 3-6, 10-13, 17-20, and 24-27, and methotrexate IT on days 10 and 24.
POST-INDUCTION THERAPY: Patients classified as standard risk are randomized to 1 of 2 arms. Patients with high risk are assigned to Arm C.
ARM A:
CONSOLIDATION BLOCK 1: Patients receive imatinib mesylate PO QD or BID on days 1-21, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 1, high dose methotrexate IV over 24 hours on day 1, vincristine sulfate IV over 1 minute on days 1 and 6, dexamethasone PO BID or IV on days 1-5, cyclophosphamide IV over 30-60 minutes on days 2-4, leucovorin calcium or levoleucovorin PO or IV on days 3 and 4, high dose cytarabine IV over 3 hours and pegaspargase or calaspargase pegol IV over 1-2 hours on day 5, and filgrastim SC or IV on days 7-11 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 2: Patients receive imatinib mesylate PO QD or BID on days 1-21, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 1, high dose methotrexate IV over 24 hours on day 1, dexamethasone PO BID or IV on days 1-5, vincristine sulfate IV over 1 minute on days 1 and 6, ifosfamide IV over 1 hour on days 2-4, leucovorin calcium or levoleucovorin PO or IV on days 3 and 4, dexrazoxane hydrochloride IV over 15 minutes and daunorubicin hydrochloride IV over 1-15 minutes on day 5, pegaspargase or calaspargase pegol IV over 1-2 hours on day 6, and filgrastim SC or IV on days 7-11 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 3: Patients receive imatinib mesylate PO QD or BID on days 1-21, high dose cytarabine IV over 3 hours on days 1-3, dexamethasone PO BID or IV on days 1-5, etoposide IV over 1-2 hours on days 3-5, methotrexate IT, cytarabine IT, and therapeutic hydrocortisone IT on day 5, pegaspargase or calaspargase pegol IV over 1-2 hours on day 6, and filgrastim SC or IV on days 7-11 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 1 PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-35, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 15 minutes, and doxorubicin IV over 3-15 minutes on days 8, 15, 22, and 29, and pegaspargase or calaspargase pegol IV over 1-2 hours on day 8 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 1 PART 2: Patients receive imatinib mesylate PO QD on days 36-63, cyclophosphamide IV over 30-60 minutes on day 36, thioguanine PO on days 36-49, cytarabine IV over 1-30 minutes or SC on days 38-41 and 45-48, and methotrexate IT on days 38 and 45in the absence of disease progression or unexpected toxicity.
INTERIM MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-28, methotrexate PO on days 1, 8, 15, and 22, and mercaptopurine PO on days 1-28 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 2 PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-35, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 15 minutes, and doxorubicin IV over 3-15 minutes on days 8, 15, 22, and 29, and pegaspargase or calaspargase pegol IV over 1-2 hours on day 8 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION 2 PART 2: Patients receive imatinib mesylate PO QD on days 36-49, cyclophosphamide IV over 30-60 minutes on day 36, thioguanine PO on days 36-49, cytarabine IV over 1-30 minutes or SC on days 36-39 and 43-46, and methotrexate IT on days 36 and 43 in the absence of disease progression or unexpected toxicity.
MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-84, methotrexate PO once weekly (QW) and IT on days 1 and 43 of cycles 1, 2, and 3, and mercaptopurine PO on days 1-84. Cycles with imatinib mesylate and mercaptopurine repeat every 84 days for up to 104 weeks from the start of Induction IA in the absence of disease progression or unexpected toxicity.
ARM B:
INTERIM MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-63, vincristine sulfate IV over 1 minute and high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin calcium or levoleucovorin PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO on days 1-56, and methotrexate IT on days 1 and 29 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION PART 1: Patients receive imatinib mesylate PO QD or BID on days 1-28, methotrexate IT on day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine sulfate IV over 1 minute, dexrazoxane hydrochloride IV over 15 minutes, and doxorubicin IV over 3-15 minutes on days 1, 8, and 15, and pegaspargase or calaspargase pegol IV over 1-2 hours or IM on day 4 in the absence of disease progression or unexpected toxicity.
DELAYED INTENSIFICATION PART 2: Patients receive imatinib mesylate PO QD on days 29-56, cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, methotrexate IT on days 29 and 36, vincristine sulfate IV over 1 minute on days 43 and 50, and pegaspargase or calaspargase pegol IV over 1-2 hours on day 43 in the absence of disease progression or unexpected toxicity.
INTERIM MAINTENANCE WITH CAPIZZI METHOTREXATE: Patients receive imatinib mesylate PO QD or BID on days 1-56, vincristine sulfate IV over 1 minute and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase or calaspargase pegol IV over 1-2 hours on days 2 and 23 in the absence of disease progression or unexpected toxicity.
MAINTENANCE: Patients receive imatinib mesylate PO QD or BID on days 1-84, vincristine sulfate IV over 1 minute on days 1, 29, and 57, prednisolone PO BID (or methylprednisolone IV for cycle 1 and 2) on days 1-5, 29-33, and 57-61, mercaptopurine PO on days 1-84, methotrexate PO QW, and methotrexate IT on day 1 (and day 29 for cycle 1 and 2). Cycles repeat every 84 days for up to 104 weeks from the start of Induction IA in the absence of disease progression or unexpected toxicity.
ARM C:
CONSOLIDATION BLOCK 1: Patients receive imatinib mesylate, methotrexate, cytarabine, therapeutic hydrocortisone, high dose methotrexate, vincristine sulfate, dexamethasone, leucovorin calcium or levoleucovorin, high dose cytarabine, and pegaspargase or calaspargase pegol as in Arm A Consolidation Block 1, and filgrastim SC or IV on day 7 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 2: Patients receive imatinib mesylate, methotrexate, cytarabine, therapeutic hydrocortisone, high dose methotrexate, dexamethasone, vincristine sulfate, ifosfamide, leucovorin calcium or levoleucovorin, dexrazoxane hydrochloride, daunorubicin hydrochloride, pegaspargase or calaspargase pegol, and filgrastim as Arm A Consolidation Block 2 in the absence of disease progression or unexpected toxicity.
CONSOLIDATION BLOCK 3: Patients receive imatinib mesylate, dexamethasone, etoposide, methotrexate, cytarabine, therapeutic hydrocortisone, pegaspargase or calaspargase pegol, and filgrastim as in Arm A Consolidation Block 3, and high dose cytarabine IV over 3 hours on days 1-2 in the absence of disease progression or unexpected toxicity.
HSCT: Patients undergo HSCT on day 0. Patients who do not proceed to HSCT receive Delayed Intensification 1, Interim Maintenance, Delayed Intensification 2, and Maintenance as in Arm A.
POST-HSCT: Patients receive imatinib mesylate PO QD or BID starting on days 56-365 in the in the absence of disease progression or unexpected toxicity.
After completion of study treatment, patients are followed up every year for 3 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 475
-
For patients enrolled on APEC14B1 prior to enrollment on AALL1631, the required diagnostic bone marrow sample has been fulfilled
- For patients who have not previously enrolled on APEC14B1 prior to enrollment on AALL1631, a baseline diagnostic sample (or peripheral blood sample with blasts if marrow sample unavailable) must be available to develop an MRD probe
- In addition, laboratory reports detailing evidence of BCR::ABL1 fusion or ABL-class fusion must be submitted for rapid central review within 72 hours of study enrollment
-
>= 1 year (365 days) and =< 21 years at ALL diagnosis
-
Ph+ (BCR::ABL1 fusion): newly diagnosed de novo ALL (B-ALL or T-ALL) or mixed phenotypic acute leukemia (MPAL meeting 2016 World Health Organization [WHO] definition) with definitive evidence of BCR::ABL1 fusion by karyotype, fluorescence in situ hybridization (FISH) and/or molecular methodologies
-
ABL-class fusion: newly diagnosed B-ALL with definitive evidence of ABL-class fusions. ABL-class fusions are defined as those involving the following genes: ABL1, ABL2, CSF1R, PDGFRB, PDGFRA. Methods of detection include fluorescence in-situ hybridization ([FISH], e.g. using break-apart or colocalization signals probes), multiplex or singleplex reverse-transcription polymerase chain reaction (RT-PCR), whole transcriptome or panel-based RNA-sequencing (e.g. TruSight RNA Pan-Cancer Panel; Illumina, San Diego, California [CA], United States of America [USA] or similar)
-
Ph+ patients must have previously started Induction therapy, which includes vincristine, a corticosteroid, pegaspargase, with or without anthracycline, and/or other standard cytotoxic chemotherapy
-
Ph+ patients have not received more than 14 days of multiagent Induction therapy beginning with the first dose of vinCRIStine
-
Ph+ patients may have started imatinib prior to study entry but have not received more than 14 days of imatinib
-
ABL-class fusion patients must have previously completed the 4 or 5 weeks of multiagent Induction chemotherapy (Induction IA phase)
-
ABL-class fusion patients may have started imatinib during Induction IA, at the same time of or after the first vinCRIStine dose
-
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2
-
Direct bilirubin =< 2.0 mg/dL
-
Shortening fraction of >= 27% by echocardiogram
-
Ejection fraction of >= 50% by radionuclide angiogram or echocardiogram
-
Corrected QT interval, QTc < 480 msec
- Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis, before study enrollment
-
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or serum creatinine within normal limits based on age/gender, as follows:
- 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)
- 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)
- 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)
- 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)
- 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)
- >= 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)
-
Known history of chronic myelogenous leukemia (CML)
-
ALL developing after a previous cancer treated with cytotoxic chemotherapy
-
Active, uncontrolled infection, or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
-
Down syndrome
-
Pregnancy and breast feeding
- 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 treatment according to protocol
-
Patients with congenital long QT syndrome, history of ventricular arrhythmias or heart block
-
Prior treatment with dasatinib, or any TKI other than imatinib
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Calaspargase Pegol See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Cyclophosphamide See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Cytarabine See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Daunorubicin Hydrochloride See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Dexamethasone See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Dexrazoxane Hydrochloride See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Doxorubicin See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Etoposide See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Filgrastim See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Ifosfamide See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Imatinib Mesylate See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Laboratory Biomarker Analysis See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Leucovorin Calcium See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Levoleucovorin See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Mercaptopurine See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Methotrexate See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Methylprednisolone See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Pegaspargase See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Prednisolone See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Questionnaire Administration See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Therapeutic Hydrocortisone See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Thioguanine See Detailed Description Arm A (imatinib mesylate, EsPhALL chemotherapy) Vincristine Sulfate See Detailed Description Arm B (imatinib mesylate, COG/BFM chemotherapy) Calaspargase Pegol See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Cyclophosphamide See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Cytarabine See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Dexamethasone See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Dexrazoxane Hydrochloride See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Doxorubicin See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Imatinib Mesylate See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Laboratory Biomarker Analysis See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Leucovorin Calcium See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Levoleucovorin See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Mercaptopurine See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Methotrexate See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Methylprednisolone See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Pegaspargase See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Prednisolone See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Questionnaire Administration See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Thioguanine See Detailed Description. Arm B (imatinib mesylate, COG/BFM chemotherapy) Vincristine Sulfate See Detailed Description. Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Allogeneic Hematopoietic Stem Cell Transplantation See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Calaspargase Pegol See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Cyclophosphamide See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Cytarabine See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Daunorubicin Hydrochloride See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Dexamethasone See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Dexrazoxane Hydrochloride See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Doxorubicin See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Etoposide See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Filgrastim See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Ifosfamide See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Imatinib Mesylate See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Laboratory Biomarker Analysis See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Leucovorin Calcium See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Levoleucovorin See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Mercaptopurine See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Methotrexate See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Methylprednisolone See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Pegaspargase See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Prednisolone See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Questionnaire Administration See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Therapeutic Hydrocortisone See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Thioguanine See Detailed Description Arm C (imatinib mesylate, EsPhALL chemotherapy, HSCT) Vincristine Sulfate See Detailed Description
- Primary Outcome Measures
Name Time Method Disease free survival (DFS) of Randomized Arms (standard risk [SR] Philadelphia chromosome [Ph+] acute lymphoblastic leukemia [ALL] patients) Up to 3 years Three-year DFS and 95% confidence intervals (CI) of SR Ph+ ALL patients treated continuous imatinib mesylate with high risk Children's Oncology Group (COG)-ALL chemotherapy backbone or more intensive European (Es)PhALL chemotherapy backbone.
- Secondary Outcome Measures
Name Time Method DFS on Randomized Arms (SR Ph+ ALL and ABL-class fusion positive patients) Up to 3 years Three-year DFS (time from randomization to relapse, second malignancy, or death in complete remission) and 95% CI of SR pediatric Ph+ and ABL-class fusion positive patients treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.
Feasibility of post hematopoietic stem cell transplantation (HSCT) imatinib mesylate administration after allogenic HSCT in high risk Ph+ ALL patients Up to 2 years The proportion of patients who receive at least 75% of intended doses.
Event free survival (EFS) of high risk pediatric Ph+ ALL patients treated with EsPhALL chemotherapy, HSCT in first complete remission, and post-HSCT imatinib mesylate Up to 3 years Three-year EFS and 95% CI for high risk pediatric Ph+ ALL patients treated with EsPhALL chemotherapy, HSCT in first complete remission, and post-HSCT imatinib mesylate. EFS is defined as the time from the date of bone marrow for minimal residual disease (MRD) assessment at end-IB to first event (resistant disease \[MRD \>= 10-2 or morphologic residual disease at end of consolidation block 3\], relapse, progressive disease \[i.e., MRD \>= 10-2 at two post-HSCT time points separated by at least 2 weeks\], second malignancy, or death in complete remission), or time to last follow-up for patients without events.
Incidence of grade 3 or higher infections in standard risk Ph+ ALL patients in the two randomized arms Up to 3 years Evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The rate of infections during the post IB/pre-maintenance phases of treatment will be described for each randomization group.
EFS of all Ph+ patients Up to 3 years Three-year EFS and 95% CI for Ph+ ALL patients. EFS here is defined as the time from enrollment until resistant disease, relapse, progressive disease post-HSCT, second malignant, or death, whichever occurs first.
Overall survival (OS) of all Ph+ patients Up to 3 years Three-year OS and 95% CI for Ph+ ALL patients. OS is defined as the time from study enrollment to death from any cause.
OS of SR Ph+ patients Up to 3 years Three-year OS (time from randomization to death from any cause) and 95% CI of SR pediatric Ph+ patients
OS of SR Ph+ patients by randomization group Up to 3 years Three-year OS (time from randomization to death from any cause) and 95% CI of SR pediatric Ph+ patients by randomization group: treated with continuous imatinib combined with either a high-risk COG-ALL chemotherapy backbone or the more intensive EsPhALL chemotherapy backbone.
OS of high risk Ph+ patients Up to 3 years Three-year OS (time from the date of MRD assessment at end-IB to death from any cause) and 95% CI of HR pediatric Ph+ patients.
EFS of all eligibility ABL-class fusion positive ALL patients Up to 3 years Three-year EFS (time from enrollment until resistant disease, relapse, progressive disease post-HSCT, second malignancy, or death, whichever occurs first) and 95% CI of ABL-class fusion positive patients.
OS of all eligibility ABL-class fusion positive ALL patients Up to 3 years Three-year OS (the time from study enrollment to death from any cause) and 95% CI of ABL-class fusion positive patients.
Trial Locations
- Locations (226)
Children's Hospital of Alabama
🇺🇸Birmingham, Alabama, United States
USA Health Strada Patient Care Center
🇺🇸Mobile, Alabama, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Banner Children's at Desert
🇺🇸Mesa, Arizona, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Kaiser Permanente Downey Medical Center
🇺🇸Downey, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Scroll for more (216 remaining)Children's Hospital of Alabama🇺🇸Birmingham, Alabama, United States