|Phase II||Treatment||Approved-not yet active||16 to 39||NCI, Other||CDR0000574230|
CALGB-10403, ECOG C10403, SWOG C10403, NCT00558519
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia.
Further Study Information
- To describe the outcomes (i.e., complete response rate, event-free survival, disease-free survival [DFS], and overall survival [OS]) of adolescents and young adults with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a pediatric chemotherapy regimen by adult hematologists/oncologists at multiple sites.
- To explore the feasibility of extending the "pediatric approach" to adult patients up to 40 years of age.
- To estimate the DFS and OS of these patients.
- To describe the toxicities observed in these patients.
- To compare the outcomes of patients treated on this protocol with appropriate similar patients (by age and disease characteristics) treated by pediatric oncologists on protocol COG-AALL0232.
- To evaluate the adherence of adult hematologists/oncologists and their patients to a "pediatric" ALL treatment regimen and identify reasons for variances.
- To analyze and describe the outcomes of patients treated on this study according to pretreatment characteristics such as age, gender, white blood cell count, other hematologic parameters, blood chemistry, immunophenotype, cytogenetics and molecular genetic characteristics, and treatment variables such as treatment site (academic center or community), and protocol adherence.
- To analyze and describe the outcomes of patients treated on this study according to baseline psychosocial characteristics, demographics, and family support.
OUTLINE: This is a multicenter study.
- Remission induction therapy: Patients receive intrathecal (IT) cytarabine on day 1; vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally twice daily on days 1-28; daunorubicin hydrochloride IV on days 1, 8, 15, and 22; pegaspargase IV or intramuscularly (IM) on day 4 or 5 or 6; and IT methotrexate on days 8 and 29*. Patients undergo bone marrow aspirate (BMA) and biopsy on day 29 to assess induction response and minimal residual disease status. Patients with M1 marrow (< 1% lymphoblasts) proceed to remission consolidation therapy. Patients with M2 marrow (> 5% but < 25% lymphoblasts) proceed to extended remission induction therapy. Patients with M3 marrow are removed from protocol therapy.
NOTE: *Patients with CNS3 disease also receive IT methotrexate on days 15 and 22.
- Extended remission induction therapy: Patients receive prednisone IV or orally twice daily on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM or IV on day 4 or 5 or 6; and daunorubicin hydrochloride IV on day 1. Patients undergo BMA and biopsy on day 15. Patients with M1 marrow proceed to remission consolidation therapy. Patients with M2 or M3 bone marrow are removed from protocol therapy.
- Remission consolidation therapy: Patients receive cyclophosphamide IV on days 1 and 29; cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; pegaspargase IM or IV on days 15 and 43; and IT methotrexate on days 1, 8, 15*, and 22*. Once blood counts recover, patients proceed to interim maintenance therapy.
NOTE: *Patients with CNS3 disease do not receive IT methotrexate on days 15 and 22.
- Interim maintenance therapy: Patients receive vincristine IV and methotrexate (Capizzi methotrexate) IV on days 1, 11, 21, 31, and 41; pegaspargase IM or IV on days 2 and 22; and IT methotrexate on days 1 and 31. Once blood counts recover (ANC ≥ 750/mm^3 and platelet count ≥ 75,000/mm^3), patients proceed to delayed intensification therapy.
- Delayed intensification therapy: Patients receive vincristine IV on days 1, 8, 15, 43, and 50; dexamethasone IV or orally twice daily on days 1-7 and 15-21; doxorubicin hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV on day 4 or 5 or 6 AND day 43; cyclophosphamide IV on day 29; cytarabine IV or SC on days 29-32 and 36-39; oral thioguanine on days 29-42; and IT methotrexate on days 1, 29, and 36. Once blood counts recover, patients proceed to maintenance therapy.
- Maintenance therapy: Patients receive vincristine IV on days 1, 29, and 57; dexamethasone IV or orally twice daily on days 1-5, 29-33, and 57-61; mercaptopurine orally on days 1-84; IT methotrexate on day 1*; and oral methotrexate on days 8, 15, 22, 29**, 36, 43, 50, 57, 64, 71, and 78.
Treatment repeats every 12 weeks for 2 years from the start of interim maintenance (for female patients) or 3 years from the start of interim maintenance (for male patients).
NOTE: *IT methotrexate is also given on day 29 of the first 4 courses of maintenance therapy.
NOTE: **Oral methotrexate is held on day 29 of the first 4 courses of maintenance therapy (when IT methotrexate is given).
- Radiotherapy: During the first course of maintenance therapy, patients with testicular disease undergo concurrent radiotherapy to the testes 5 days a week for 2.5 weeks (total dose 2400 cGy given in 12 daily fractions); patients with CNS3 disease undergo concurrent cranial radiotherapy 5 days a week for 2 weeks (total dose of 1800 cGy given in 10 daily fractions); and patients with T-cell ALL undergo concurrent cranial radiotherapy (total dose of 2400 cGy given in 10 daily fractions) 5 days a week for 2 weeks.
Patients may complete surveys at the end of courses 1, 2, and 4, at the end of all protocol treatment, and at 6 and 18 months after the end of all protocol treatment.
After completion of study treatment, patients are followed every 1-3 months for 3 years and then every 6 months for 7 years.
- Newly diagnosed acute lymphoblastic leukemia (ALL)
- B-precursor or T-precursor ALL
- No Burkitt type leukemia (FAB L3; SIg positive; t(8;14) or variant)
- No known Ph+ ALL at time of diagnosis
- Enrollment on CALGB-C10001 (or its successor trial) for CALGB patients with Philadelphia-positive ALL take priority over enrollment on this protocol
- Patients enrolled on this study but are later found to meet the following criteria for Ph+ ALL eligibility criteria for protocol CALGB-C10001 (or its successor trial) are removed from this study and enrolled on CALGB-C10001 (or its successor study):
- BCR-ABL fusion transcript determined by FISH or RT-PCR
- t(9;22)(q34;q11) or variant determined by cytogenetics
- All CALGB patients are required to participate in CALGB-8461
- All SWOG patients are required to participate in SWOG-9007
- ECOG performance status 0-2
- No Down syndrome
PRIOR CONCURRENT THERAPY:
- No prior therapy for acute leukemia except emergency therapy (i.e., corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys
- Single-dose intrathecal cytarabine is allowed prior to registration for patient convenience provided systemic chemotherapy begins within 72 hours of intrathecal therapy
- Prior steroid therapy allowed
Trial Lead Organizations/Sponsors
Cancer and Leukemia Group BNational Cancer Institute
Eastern Cooperative Oncology Group
Southwest Oncology Group
|Richard A. Larson||Study Chair|
|John C. Grecula|
|Selina M. Luger||Study Chair|
|Anjali Advani||Study Chair|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00558519
Information obtained from ClinicalTrials.gov on February 14, 2013
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