S0333 Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
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), and giving the drugs in different combinations may kill more cancer cells.
PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.
Full description
OBJECTIVES:
Primary
- Determine the probability of 1-year continuous complete remission in patients with newly diagnosed acute lymphoblastic leukemia treated with first induction chemotherapy comprising daunorubicin, vincristine, prednisone, and pegaspargase; and second induction chemotherapy comprising high-dose cytarabine and mitoxantrone.
Secondary
- Determine the frequency and severity of toxic effects of these induction regimens followed by consolidation therapy comprising cyclophosphamide, cytarabine, mercaptopurine, and methotrexate and maintenance chemotherapy comprising mercaptopurine, methotrexate, vincristine, doxorubicin, dexamethasone, cyclophosphamide, thioguanine, and cytarabine in these patients.
Other objectives (if funding allows):
- To evaluate in a preliminary manner the significance of detecting minimal residual disease as a prognostic factor for survival and relapse-free survival of patients receiving chemotherapy
- To evaluate in a preliminary manner the pattern of gene expression of patients entered onto the trial and its relationship to cytogenetics/FISH risk classification, overall survival, and relapse-free survival
OUTLINE: This is a multicenter study.
- First induction chemotherapy: Patients receive daunorubicin IV on days 1-3; vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally on days 1-28, followed by a taper to day 35; and pegaspargase IV or subcutaneously (SC) on day 15. Patients with CNS leukemia also receive methotrexate intrathecally (IT) or intraventricularly twice weekly and oral leucovorin calcium four times daily for 4 doses after each administration of methotrexate. When blasts are no longer present in the spinal fluid, patients receive methotrexate IT or intraventricularly once weekly for 4 weeks and then once monthly for 1 year.
Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status or those with resistant disease proceed to second induction therapy.
- Second induction chemotherapy: Patients receive high-dose cytarabine IV on days 1-5; mitoxantrone IV on day 3; and filgrastim (G-CSF) SC or IV beginning on day 7 and continuing until blood counts recover. Patients with CNS leukemia also receive methotrexate and leucovorin calcium as in first induction chemotherapy.
Patients are reevaluated on day 28. Patients who achieve A1 bone marrow status and B1 peripheral blood status with no extramedullary disease (other than CNS involvement) proceed to consolidation chemotherapy. Patients with resistant disease OR Philadelphia chromosome- or BCR/ABL-positive disease are removed from the study after receiving double induction chemotherapy.
- Consolidation chemotherapy: Patients receive cyclophosphamide IV on days 1, 15, and 29; cytarabine IV on days 2-5 and 16-19; oral mercaptopurine on days 1-28; and methotrexate IT or intraventricularly on days 2, 9, 16, and 23. Patients with CNS leukemia also undergo cranial radiotherapy once daily, 5 days a week, for 2 weeks.
Patients in complete remission proceed to maintenance chemotherapy.
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Maintenance chemotherapy:
- Course 1: Patients receive oral mercaptopurine on days 1-63 and oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, and 57. Patients proceed to course 2 after blood counts recover.
- Course 2: Patients receive vincristine IV and doxorubicin IV on days 1, 8, 15, and 22 and oral dexamethasone on days 1-28. Patients proceed to course 3 after blood counts recover.
- Course 3: Patients receive cyclophosphamide IV on day 1; oral thioguanine on days 1-14; and cytarabine IV on days 3-6 and 10-13. Patients proceed to course 4 after blood counts recover.
- Course 4: Patients receive oral mercaptopurine once daily for 2 years and oral methotrexate once weekly for 2 years.
Treatment continues in the absence of disease relapse or unacceptable toxicity.
After completion of study therapy, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
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Morphologically confirmed acute lymphoblastic leukemia (ALL), meeting any of the following criteria:
- FAB class L1 or L2 disease
- Mixed lineage ALL
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Ph-negative/BCR/ABL-negative
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Newly diagnosed disease
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Patients with the following diagnoses are not eligible:
- FAB class L3 ALL
- Non-Hodgkin's lymphoma
- Chronic myelogenous leukemia in lymphoid blast crisis
- Mixed lineage acute myeloid leukemia
- Acute minimally differentiated myeloid leukemia (M0)
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Must be registered on protocols SWOG-9007 AND SWOG-S9910
PATIENT CHARACTERISTICS:
Age
- 18 to 64
Performance status
- Zubrod 0-3
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
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No chronic liver disease
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Hepatitis panel, including hepatitis B and C, negative
- History of hepatitis A with positive antibody allowed
Renal
- Creatinine ≤ 1.5 times upper limit of normal OR
- Creatinine clearance > 60 mL/min
Cardiovascular
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Left ventricular function normal
- Ejection fraction ≥ 50% by MUGA or 2-dimensional echocardiogram
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No symptomatic congestive heart failure
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No coronary artery disease
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No cardiomyopathy
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No uncontrolled arrhythmia
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception
- HIV negative
- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
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No prior remission induction chemotherapy for ALL
- Prior hydroxyurea to control WBC count allowed
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- No other prior treatment for ALL
Trial design
Primary purpose
Allocation
Interventional model
Masking
79 participants in 1 patient group
Trial contacts and locations
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Data sourced from clinicaltrials.gov
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