Clinical trial NCT00039130
Conditions: Leukemia Lymphoma
Keywords: untreated adult acute lymphoblastic leukemia L3 adult acute lymphoblastic leukemia stage I adult Burkitt lymphoma stage III adult Burkitt lymphoma stage IV adult Burkitt lymphoma contiguous stage II adult Burkitt lymphoma noncontiguous stage II adult Burkitt lymphoma
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2002-05-01; Completion date: 2014-10-01
Enrollment: 105 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the numbers of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. Combining chemotherapy with rituximab and filgrastim may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with chemotherapy and filgrastim in treating patients who have Burkitt's lymphoma or Burkitt's leukemia.

Detailed description:
OBJECTIVES:

* Determine the complete response rate in patients with previously untreated Burkitt's lymphoma or Burkitt's leukemia treated with rituximab and high-intensity chemotherapy with filgrastim (G-CSF) support.
* Determine the progression-free and overall survival of patients treated with this regimen.
* Determine the feasibility and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease (leukemia vs lymphoma).

* Course 1: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5 and oral prednisone on days 1-7. Allopurinol PO will be given on days 1-14.
* Courses 2, 4, and 6: Patients receive ifosfamide IV over 1 hour daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV over 15 minutes every 6 hours on day 2; cytarabine IV over 2 hours on days 4 and 5 and etoposide IV over 1 hour daily on days 4 and 5; oral dexamethasone daily on days 1-5; and methotrexate and cytarabine intrathecally (IT) on day 1. During course 2, patients receive rituximab IV over 1-4 hours on days 8, 10, and 12. During courses 4 and 6, patients receive rituximab IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 7 and continuing until blood counts recover.
* Courses 3, 5, and 7: Patients receive cyclophosphamide IV over 5-15 minutes daily on days 1-5; vincristine IV over 10 minutes and methotrexate IV over 24 hours on day 1; leucovorin calcium IV every 6 hours on day 2; doxorubicin IV daily on days 4 and 5; oral dexamethasone daily on days 1-5; methotrexate and cytarabine IT on day 1; and rituximab IV over 1 hour on day 8. Patients also receive G-CSF as in courses 2, 4, and 6. After course 3, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 100 patients (50 per stratum) will be accrued for this study within 3 years.

Arms: arm 1: Cycle1: Cyclophosphamide 100 mg/m\^2/day (d) IV (d 1-5), Prednisone 60 mg/m\^2/d oral (d 1-7), Allopurinal 300 mg/d oral (d 1-14) Cycle 2, 4 \& 6 (21 day): Ifosfamide 800 mg/m\^2/d (d 1-5), Dexamethasone 10 mg/m\^2/d (d1-5), Methotrexate 150 mg/m\^2 load, then 1.35 g/m\^2 over 23.5 h (d 1), Leucovorin 25 mg/m\^2 36 h after methotrexate (d 2) then 10 mg/m\^2 every 6 h, Vincristine 2 mg push (d 1), Cytarabine 1000 mg/m\^2/d over 2 h (d 4-5), Etoposide 80 mg/m\^2.d over 1 h (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 50 mg/m\^2 d 8 cycle 2 only, 375 mg/m\^2/d (d 10, 12 cycle 2, d 8 cycle 4 \& 6) Cycle 3, 5 \& 7 (21 day): Cyclophosphamide 200 mg/m\^2/day (d) IV (d 1-5), Dexamethasone 10 mg/m\^2/d (d1-5), Methotrexate 150 mg/m\^2 load, then 1.35 g/m\^2 over 23.5 h (d 1), Leucovorin 50 mg/m\^2 36 h after methotrexate (d 2) then 10 mg/m\^2 every 6 h, Vincristine 2 mg push (d 1), Doxorubicin 25 mg/m\^2/d (d 4-5), Filgrastim 5 mg/kg/d (d 7-21 as needed), Rituximab 375 mg/m\^2/d (d 8)
Interventions: intervention 1: filgrastim intervention 2: rituximab intervention 3: cyclophosphamide intervention 4: cytarabine intervention 5: dexamethasone intervention 6: doxorubicin hydrochloride intervention 7: etoposide intervention 8: ifosfamide intervention 9: leucovorin calcium intervention 10: methotrexate intervention 11: prednisone intervention 12: vincristine sulfate intervention 13: Allopurinol
Intervention descriptions: intervention 1: 5 ug/kg/day sub Q injection day 7 until ANC\>5000/ul courses II-VII intervention 2: Day 8 course II 50 mg/sq m IV infusion: d 8 course IV \& VI 375mg/sq m IV Day 10 course II: 325 mg/sq m IV infusion Day 12 course II: 375 mg/sq m IV infusion intervention 3: 200 mg/sq m/day IV infusion over 5-15 min days 1-5, courses I, III, V, VII intervention 4: 1 g/sq m/day IV infusion Days 4 \& 5, courses II, IV, VI intervention 5: 10mg/sq m PO or IV Days 1-5 courses II-VII intervention 6: 25 mg/sq m/day IV infusion Days 4 \& 5 courses III,V, VII intervention 7: 80 mg/sq m/day IV infusion Days 4 \& 5 courses II, IV, VI intervention 8: 800 mg/sq m/day IV infusion Days 1-5 courses II, IV, VI intervention 9: 25mg/sq m IV infusion over 15 min then 10 mg IV q 6 hrs until serum MTX \<10nM, courses II-VII intervention 10: 1.5 g/sq m IV infusion Day 1 courses II-VII intervention 11: 60 mg/sq m PO/day Days 1-7 course I intervention 12: 2 mg IV push Day 1 courses II-VII intervention 13: 300 mg/day PO Days 1-14, course I

Protocol documents: