This trial is active, not recruiting.

Condition leukemia
Treatments filgrastim, cyclophosphamide, cytarabine, daunorubicin, dexamethasone, doxorubicin, leucovorin, mercaptopurine, methotrexate, mitoxantrone, asparaginase, prednisone, thioguanine, vincristine, radiation therapy, allopurinol, bactrim
Phase phase 2
Sponsor Southwest Oncology Group
Collaborator National Cancer Institute (NCI)
Start date April 2005
End date November 2010
Trial size 79 participants
Trial identifier NCT00109837, CDR0000426447, S0333, U10CA032102


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
Induc 1: Allopurinol; Daunorubicin; Vincristine; Prednisone; asparaginase; Bactrim Induc 2: Allopurinol; cytarabine; Dexamethasone; filgrastim; mitoxantrone; Methotrexate; leucovorin Consol: Cyclophosphamide; cytarabine; 6-mercaptopurine; Methotrexate; filgrastim Maint:Course 1: 6-mercaptopurine; Methotrexate Course 2: Vincristine; doxorubicin; Dexamethasone Course 3: Cyclophosphamidee; thioguanine; cytarabine Course 4: 6-mercaptopurine; methotrexate
As needed per physician discretion
Cyclophosphamide Consolidation: 650 mg/m2; IV; days 1, 15, 29 Post-consolidation course 3: 650 mg/m2; IV; day 1
Induction 2: 3 g/m2; IV over 3 hrs; days 1-5 Consolidation: 75 mg/m2/d; IV push; days 2-5 and 16-19 Post-consolidation course 3: 75 mg/m2/d; IV push; days 3-6 and 10-13
Induction: 60 mg/m2/d; IV; days 1, 2, and 3
Induction 2: 0.1% QID; eye drops; days 1-6 Post consolidation course 2: 10 mg/m2/d; PO; days 1-28
Post consolidation: 25 mg/m2; IV; days 1, 8, 15, and 22
For CNS during induction: 5 mg every 6 hrs for 4 doses; PO; days 1, 4, 8, 11, etx.; after methotrexate if WBC < 3,000
Consolidation: 60 mg/m2; PO; days 1-28 Post-consolidation course 1: 60 mg/m2/d; PO; days 1-63 Post-consolidation course 4: 60 mg/m2/d; PO; daily for 2 yrs
Consolidation: 12 mg; intrathecal or intraventricularly; days 2, 9, 16, and 23 Post-consolidation course 1: 20 mg/m2/wk; PO; days 1, 8 15, 22, 29, 36, 43, 50, 57 Post-consolidation course 4: 20 mg/m2; PO; weekly for 2 yrs
Induction 2: 80 mg/m2; IV; day 3
Induction: 2,000 IU/m2; IM or IV; day 15
Induction: 60 mg/m2/d; PO or IV; days 1-35
Post-consolidation course 3: 60 mg/m2/d; PO; days 1-14
Induction: 1.4 mg/m2/d (2 mg max); IV; days 1, 8, 15, 22
radiation therapy
For CNS during consolidation: cranial radiation after blasts are no longer present in spinal fluid. Total dose of 1800 cGy over 2 wks in 10 fractions of 180 cGy 5 days/wk.
300 mg/d PO Days 1-7
1 double strenth tablet 2x/d, 2x/wk, PO, begin with prednisone

Primary Outcomes

Continuous Complete Remission at 1 Year
time frame: After induction, after consolidation, every 3 months during maintenance, and every three months after off treatment for up to a year

Secondary Outcomes

time frame: Patients were assessed for adverse events after the induction cycle

Eligibility Criteria

Male or female participants from 18 years up to 64 years old.

DISEASE CHARACTERISTICS: - Morphologically confirmed acute lymphoblastic leukemia (ALL), meeting any of the following criteria: - FAB class L1 or L2 disease - Mixed lineage ALL - Ph-negative/BCR/ABL-negative - Newly diagnosed disease - 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) - 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 - No chronic liver disease - 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 - Left ventricular function normal - Ejection fraction ≥ 50% by MUGA or 2-dimensional echocardiogram - No symptomatic congestive heart failure - No coronary artery disease - No cardiomyopathy - 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 - 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

Additional Information

Official title A Phase II Study of Double Induction Chemotherapy for Newly Diagnosed Non-L3 Adult Acute Lymphoblastic Leukemia With Investigation of Minimal Residual Disease and Risk of Relapse Following Maintenance Chemotherapy
Principal investigator Frederick R. Appelbaum, MD
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. - 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.
Trial information was received from ClinicalTrials.gov and was last updated in February 2014.
Information provided to ClinicalTrials.gov by Southwest Oncology Group.