Clinical trial NCT03020030: Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents
Official title: Treatment of Newly Diagnosed Acute Lymphoblastic Leukemia in Children and Adolescents
Conditions: Acute Lymphoblastic Leukemia, Pediatric
Summary: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The cancer comes from a cell in the blood called a lymphocyte. Normal lymphocytes are produced in the bone marrow (along with other blood cells) and help fight infections. In ALL, the cancerous lymphocytes are called lymphoblasts. They do not help fight infection and crowd out the normal blood cells in the bone marrow so that the body cannot make enough normal blood cells. ALL is always fatal if it is not treated. With current treatments, most children and adolescents with this disease will be cured.
The standard treatment for ALL involves about 2 years of chemotherapy. The drugs that are used, and the doses of the drugs, are similar but not identical for all children and adolescents with ALL. Some children and adolescents receive stronger treatment, especially during the first several months. A number of factors are used to decide how strong the treatment should be to give the best chance for cure. These factors are called "risk factors". This trial is studying the use of a new, updated set of risk factors to decide how strong the treatment will be. The study also will test a new way of dosing a chemotherapy drug called pegaspargase (which is part of the standard treatment for ALL) based on checking levels of the drug in the blood and adjusting the dose based on the levels.
Interventions:
description: Arm A: Standard/Fixed Dose Pegaspargase (2500 IU/m2 every 2 weeks) Arm B: Reduced Dose (PK-adjusted) Pegaspargase (Starting Dose: 2000 IU/m2) Arm X: Directly Assigned Standard Dose (2500 IU/m2): For all VHR and patients who decline randomization
name: Pegaspargase
type: Drug
description: Only for patients with Pegaspargase allergy or silent inactivation.
name: Erwinia asparaginase
other_name: ERWINASE®
ERWINAZE®
ERWINIA CHRYSANTHEMI
type: Drug
description: Standard of Care
name: Cyclophosphamide
other_name: CYTOXAN
type: Drug
description: Standard of Care
name: CYTARABINE
other_name: ARA-C
CYTOSAR®
CYTOSINE ARABINOSIDE
type: Drug
description: Standard of Care
name: DASATINIB
type: Drug
description: Standard of Care
name: DEXAMETHASONE
other_name: DECADRON®
DEXAMETH®
DEXONE®,
HEXADROL®,
type: Drug
description: Standard of Care
name: Dexrazoxane
other_name: Zinecard
type: Drug
description: Standard of Care
name: Doxorubicin
other_name: ADRIAMYCIN®
type: Drug
description: Standard of Care
name: ETOPOSIDE
other_name: VePesid
type: Drug
description: Standard of Care
name: HYDROCORTISONE
type: Drug
description: Standard of Care
name: LEUCOVORIN CALCIUM
type: Drug
description: Standard of Care
name: MERCAPTOPURINE
other_name: 6-MP
type: Drug
description: Standard of Care
name: METHOTREXATE
type: Drug
description: Standard of Care
name: NELARABINE
type: Drug
description: Standard of Care
name: Vincristine
other_name: Oncovin
type: Drug
Study arms:
design_group_description: Meets all the following criteria: B-ALL, Age 1-<15 years, WBC < 50,000/microliter, CNS-1 or CNS-2, no BCR-ABL1, no iAMP21, and no VHR characteristics.<br/>Treated with Induction IA (vincristine, dexamethasone, pegaspargase), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
design_group_title: Initial Low Risk (Initial LR)
design_group_type: Other
design_group_description: Meets at least one of the following criteria: Age >=15 years, WBC >=50,000/microliter, CNS-3, T-ALL, iAMP21, BCR-ABL1<br/>And: No VHR characteristics<br/>Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
design_group_title: Initial High Risk (Initial HR)
design_group_type: Other
design_group_description: Any of the following are present: IKZF1 deletion, MLL (KMT2A) rearrangement, low hypodiploidy, t(17;19)<br/>Treated with Induction IA (vincristine, dexamethasone, pegaspargase, doxorubicin + dexrazoxane), Induction IB (cyclophosphamide, cytarabine, mercaptopurine), Consolidation IA (vincristine, high-dose methotrexate + leucovorin, mercaptopurine). IT chemotherapy in all phases. Final risk group assigned by end of Consolidation IA.
design_group_title: Initial Very High Risk (Initial VHR)
design_group_type: Other
design_group_description: Initial Low Risk and Low MRD (<0.0001) at first time point (Day 32)<br/>Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:<br/>CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, methotrexate, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).<br/>All treatment completed 24 months from date of complete remission.
design_group_title: Final Low Risk (Final LR)
design_group_type: Other
design_group_description: Initial High Risk and Low MRD (<0.0001) at first time point (Day 32)<br/>Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:<br/>CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).<br/>All treatment completed 24 months from date of complete remission.
design_group_title: Final Intermediate Risk (Final IR)
design_group_type: Other
design_group_description: Initial Low Risk or Initial High Risk with High MRD (>=0.0001) at first time point (Day 32) but low MRD (<0.001) at second time point (week 10-12)<br/>Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:<br/>CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by randomization or direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by randomization or direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).<br/>All treatment completed 24 months from date of complete remission.
design_group_title: Final High Risk (Final HR)
design_group_type: Other
design_group_description: Initial VHR or any patient with high MRD (>=0.001) at second time point (week 10-12)<br/>Final Risk Group assigned at end of Consolidation IA. Subsequent therapy as follows:<br/>Consolidation IB/B-ALL (High-dose methotrexate + leucovorin, cyclophosphamide, etoposide, IT chemotherapy); Consolidation IB/T-ALL (nelararbine, cyclophosphamide, etoposide); Consolidation IC (High-dose cytarabine, etoposide, dexamethasone, pegaspargase [by direct assignment], IT chemotherapy); CNS phase (vincristine, dexamethasone, mercaptopurine, pegaspargase [by direct assignment], IT chemotherapy); Consolidation II (vincristine, dexamethasone, mercaptopurine, doxorubicin + dexrazoxane, pegaspargase [by direct assignment], IT chemotherapy); Continuation (vincristine, dexamethasone, mercaptopurine, methotrexate, IT chemotherapy).<br/>Dasatinib administered daily during all phases to pts with ABL1-class fusions. All treatment completed 24 months from date of complete remission.
design_group_title: Final Very High Risk (Final VHR)
design_group_type: Other
design_group_description: Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks at standard fixed-dose (2500 IU/m2/dose).
design_group_title: Fixed Dose Pegaspargase
design_group_type: Active Comparator
design_group_description: Final LR, IR, HR patients who consent to randomization and are assigned to receive 15 doses of pegaspargase every 2-weeks beginning at a reduced dose (2000 IU/m2/dose); subsequent doses adjusted based on nadir serum asparaginase activity (NSAA) levels, with goal of maintaining NSAA between 0.4 and 1.0 IU/mL. Closed to Enrollment.
design_group_title: Reduced Dose (PK-Adjusted) Pegaspargase
design_group_type: Experimental
design_group_description: All VHR patients, and any Final LR, IR, HR patients who decline randomization: Assigned to receive standard dosing of pegaspargase (15 doses of pegaspargase every 2-weeks at standard fixed-dose; 2500 IU/m2/dose).
design_group_title: Direct Assignment
design_group_type: Other
Sponsor: Dana-Farber Cancer Institute, Inc.
Collaborators: Servier Pharmaceuticals LLC
Drug name mappings:
name: 培门冬酶
lang: CN
name: Pegaspargase
lang: EN
name: ペグアスパルガーゼ
lang: JP
name: 门冬酰胺酶
lang: CN
name: Asparaginase (Erwinia)
lang: EN