Rituximab, Chemotherapy, and Filgrastim in Treating Patients With Burkitt's Lymphoma or Burkitt's Leukemia

Alliance for Clinical Trials in Oncology

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Leukemia

Treatments

Drug: cyclophosphamide

Drug: cytarabine

Biological: filgrastim

Drug: etoposide

Drug: vincristine sulfate

Drug: doxorubicin hydrochloride

Drug: leucovorin calcium

Drug: prednisone

Drug: ifosfamide

Drug: dexamethasone

Biological: rituximab

Drug: Allopurinol

Drug: methotrexate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00039130

CDR0000069354 (Registry Identifier)

CALGB-10002

U10CA031946 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

105 patients

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically, cytogenetically, or immunophenotypically confirmed Burkitt's leukemia or Burkitt's or Burkitt-like lymphoma
- L3 morphology surface IgG expression
- Cytogenetic evidence for t(8;14), t(8;22), or t(2;8)
Previously untreated disease except hydroxyurea for leukocytosis
CNS involvement allowed
Patients with Burkitt's leukemia or Burkitt's lymphoma with bone marrow involvement must also be enrolled on CALGB-8461
Patients with Burkitt's leukemia must also be enrolled on CALGB-9665

PATIENT CHARACTERISTICS:

Age:

16 and over

Hepatic:

Bilirubin no greater than 1.5 times upper limit of normal (ULN)

Renal:

Creatinine no greater than 1.5 times ULN

Other:

HIV negative
Not pregnant or nursing
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No concurrent interleukin-11

Chemotherapy:

See Disease Characteristics
No other concurrent chemotherapy

Endocrine therapy:

No concurrent hormonal therapy except for non-disease-related conditions (e.g., insulin for diabetes)
No concurrent steroids except for adrenal failure

Radiotherapy:

No concurrent palliative radiotherapy except whole-brain irradiation for documented CNS disease

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

105 participants in 1 patient group

Rituximab with High Intensity Chemotherapy

Experimental group

Description:

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)

Treatment: