Overview

This trial is active, not recruiting.

Conditions b-cell adult acute lymphoblastic leukemia, b-cell childhood acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia, untreated childhood acute lymphoblastic leukemia
Treatments pegaspargase, cytarabine, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, prednisone, dexamethasone, methotrexate, daunorubicin hydrochloride, mercaptopurine, thioguanine, prophylactic cranial irradiation, laboratory biomarker analysis
Sponsor Children's Oncology Group
Collaborator National Cancer Institute (NCI)
Start date February 2009
End date June 2013
Trial size 165 participants
Trial identifier NCT00866307, AALL08P1, CDR0000636174, COG-AALL08P1, NCI-2009-01169, U10CA098543

Summary

This pilot clinical trial studies the side effects of pegaspargase when given together with combination chemotherapy in treating patients with newly diagnosed high-risk acute lymphoblastic leukemia. Pegaspargase may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) together with pegaspargase may kill more cancer cells.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Cyclophosphamide IV days 1 & 29; cytarabine IV subcutaneously (SC) days 1-4, 8-11, 29-32, & 36-39; mercaptopurine PO once daily (QD) days 1-14 & 29-42; vincristine sulfate IV days 15, 22, 43, & 50; methotrexate IT days 1, 8, 15, & 22; & pegaspargase IV days 15 & 43. Int. Maint.: Vincristine sulfate IV days 1, 11, 21, 31, & 41; methotrexate IV days 1, 11, 21, 31, & 41; methotrexate IT days 1 & 31; and pegaspargase IV days 2 & 22. Delayed Intensification: Vincristine sulfate IV days 1, 8, 15, 43, & 50; dexamethasone IV or PO days 1-7 & 15-21; doxorubicin hydrochloride IV days 1, 8, & 15; cyclophosphamide IV day 29; cytarabine IV or SC days 29-32 & 36-39; thioguanine PO days 29-42; methotrexate IT days 1, 29, & 36; and pegaspargase IV days 4 & 43. Maint. begins day 57 of DI: Vincristine sulfate IV days 1, 29, & 57; prednisone PO days 1-5, 29-33, & 57-61; mercaptopurine PO days 1-84; methotrexate IT day 1; and methotrexate PO days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, & 78.
pegaspargase L-asparaginase with polyethylene glycol
Given IV
cytarabine ARA-C
Given IT and IV or SC
vincristine sulfate leurocristine sulfate
Given IV
doxorubicin hydrochloride ADM
Given IV
cyclophosphamide CPM
Given IV
prednisone DeCortin
Given IV or PO
dexamethasone Aeroseb-Dex
Given IV
methotrexate amethopterin
Given IT and PO
daunorubicin hydrochloride Cerubidin
Given IV
mercaptopurine 6-mercaptopurine
Given PO
thioguanine 6-TG
Given PO
prophylactic cranial irradiation PCI
Undergo radiation
laboratory biomarker analysis
Correlative studies
(Experimental)
Cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and methotrexate as in group A. Beginning on day 1, pegaspargase IV every 2 weeks. Patients with CNS3 disease undergo cranial radiotherapy QD for 10 days and patients with testicular disease undergo testicular radiotherapy QD for 12 days, beginning on day 1 of consolidation. Interim Maintenance: Patients receive vincristine sulfate and methotrexate as in group A. Beginning on day 1, pegaspargase IV every 2 weeks. Delayed Intensification: Vincristine sulfate, dexamethasone, doxorubicin hydrochloride, cyclophosphamide, cytarabine, thioguanine, and methotrexate as in group A. Beginning on day 1, pegaspargase IV over 1-2 hours every 2 weeks. Maint. begins day 57 of DI: Vincristine sulfate IV days 1, 29, & 57; prednisone PO days 1-5, 29-33, & 57-61; mercaptopurine PO days 1-84; methotrexate IT day 1; and methotrexate PO days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, & 78.
pegaspargase L-asparaginase with polyethylene glycol
Given IV
cytarabine ARA-C
Given IT and IV or SC
vincristine sulfate leurocristine sulfate
Given IV
doxorubicin hydrochloride ADM
Given IV
cyclophosphamide CPM
Given IV
prednisone DeCortin
Given IV or PO
dexamethasone Aeroseb-Dex
Given IV
methotrexate amethopterin
Given IT and PO
daunorubicin hydrochloride Cerubidin
Given IV
mercaptopurine 6-mercaptopurine
Given PO
thioguanine 6-TG
Given PO
prophylactic cranial irradiation PCI
Undergo radiation
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
Percentage of patients which tolerate at least 8 of the 12-14 total doses of pegaspargase assessed by Common Terminology Criteria for Adverse Events (CTCAE) version(v)4.0
time frame: Up to 28 weeks

Secondary Outcomes

Measure
Incidence of toxicity incidents assessed by CTCAE version 4.0
time frame: Up to 10 years

Eligibility Criteria

Male or female participants from 1 year up to 30 years old.

Inclusion Criteria: - Patients must be eligible for and enrolled on AALL03B1 or the successor classification study - Patients must have newly diagnosed high-risk B-precursor acute lymphoblastic leukemia (ALL) - WBC criteria - Age 1.00-9.99 years: WBC >= 50,000/uL - Age 10.00 - 30.99 years: Any WBC - Prior steroid therapy: Any WBC - Patients with testicular leukemia: Any WBC - Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine - Intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment; systemic chemotherapy must begin within 72 hours of this intrathecal therapy - Patients receiving prior steroid therapy are eligible for study; the dose and duration of previous steroid therapy should be carefully documented - 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: - Pregnant female patients are ineligible; pregnancy tests with a negative result must be obtained in all post-menarchal females; males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; lactating females must agree that they will not breastfeed a child while on this study - Patients with Down syndrome (DS) are ineligible since excessive toxicities and death have been noted for those enrolled on AALL0232 receiving the prednisone/Capizzi methotrexate (PC) arm of treatment, which is the backbone regimen for the current study

Additional Information

Official title Intensified PEG-Asparaginase in High Risk Acute Lymphoblastic Leukemia (ALL): A Pilot Study
Principal investigator ZoAnn Dreyer, MD
Description PRIMARY OBJECTIVES: I. To demonstrate that biweekly intravenous (IV) pegaspargase beginning with Consolidation and ending with completion of delayed intensification (DI) in combination with hemi-augmented BFM therapy (hABFM) is feasible and safe in children with high risk (HR) acute lymphoblastic leukemia (ALL). OUTLINE: Patients are stratified according to risk assignment (high-risk [HR]-average [day 29 minimal residual disease (MRD) < 0.01%] vs HR-high [MRD >= 0.01%, presence of central nervous system [CNS]3 leukemia, testicular disease, myeloid/mixed lineage leukemia [MLL] rearrangement, hypodiploidy, or steroid therapy within the past month]). Patients are assigned to 1 of 2 treatment groups.* (Note: *Amendment 2 [4-22-2011] requires changes in the regimens. See the changes below, after Maintenance therapy.) INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; methotrexate IT on days 8 and 29*; and pegaspargase IV over 1-2 hours on day 4. (Note: *Patients with CNS3 disease [white blood cells [(WBC)] >= 5/uL and positive for blasts on cytospin] also receive methotrexate IT on days 15 and 22.) CONSOLIDATION THERAPY (begins on day 36 of induction therapy): GROUP A (HR-AVERAGE): Patients receive cyclophosphamide IV over 1 hour on days 1 and 29; cytarabine IV over 15 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43, and 50; methotrexate IT on days 1, 8, 15*, and 22*; and pegaspargase IV over 1-2 hours on days 15 and 43. GROUP B (HR-HIGH): Patients receive cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. Patients with CNS3 disease undergo cranial radiotherapy QD for 10 days and patients with testicular disease undergo testicular radiotherapy QD for 12 days, beginning on day 1 of consolidation. (Note: *Patients with CNS3 disease [WBC >= 5/uL and positive for blasts on cytospin] do not receive methotrexate IT on days 15 and 22.) Interim maintenance (IM) therapy (begins on day 57 of consolidation): GROUP A: Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and 41; methotrexate IV over 10-15 minutes on days 1, 11, 21, 31, and 41; methotrexate IT on days 1 and 31; and pegaspargase IV over 1-2 hours on days 2 and 22. GROUP B: Patients receive vincristine sulfate and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. DI therapy (begins on day 57 of IM): GROUP A: Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; cyclophosphamide IV over 1 hour on day 29; cytarabine IV over 15 minutes or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 1, 29, and 36; and pegaspargase IV over 1-2 hours on days 4 and 43. GROUP B: Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, cyclophosphamide, cytarabine, thioguanine, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. MAINTENANCE THERAPY (MT; begins on day 57 of DI): All patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate IT on day 1; and methotrexate PO BID on days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, and 78. In both groups, MT repeats every 12 weeks until total duration of therapy is 2 years from the start of IM for female patients and 3 years from the start of IM for male patients. Patients in Group B who did not undergo radiotherapy to the brain during consolidation therapy undergo prophylactic cranial radiotherapy (CR) daily for 8 days. ([Note: *Patients in Group A also receive methotrexate IT on day 29 of courses 1-4 [no oral methotrexate]). REVISED MT (RMT): The regimen is the same as standard MT, but 2 of the doses of IT methotrexate are omitted (day 29 of courses 3 and 4).
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Children's Oncology Group.