Combination Chemotherapy and Rituximab in Treating Patients With Newly Diagnosed Burkitt's Lymphoma or Leukemia

Johns Hopkins Medicine

Status and phase

Completed

Phase 2

Conditions

Lymphoma

Leukemia

Treatments

Drug: Prednisone

Drug: Vincristine

Biological: Rituximab

Drug: Cyclophosphamide

Drug: Methotrexate

Drug: Hydrocortisone

Drug: Leucovorin

Drug: Cytarabine

Biological: Filgrastim

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00133991

P50CA096888 (U.S. NIH Grant/Contract)

P30CA006973 (U.S. NIH Grant/Contract)

NA_00035765 (Other Identifier)

J0409

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) may kill more cancer cells. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving combination chemotherapy together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with rituximab works in treating patients with newly diagnosed Burkitt's lymphoma or leukemia.

Full description

OBJECTIVES:

Primary

Determine the overall response rate, 1-year event-free survival, and overall survival of adult patients with newly diagnosed Burkitt or atypical Burkitt lymphoma or leukemia treated with dose-intensified induction therapy comprising cyclophosphamide, vincristine, prednisone, and rituximab followed by consolidation therapy comprising rituximab and high-dose cyclophosphamide.
Determine the grade 3 or higher non-hematologic toxic effects and overall tolerability of this regimen in these patients.

Secondary

Determine the 3-year event-free survival and overall survival of patients treated with this regimen.
Determine the general patterns of CNS and systemic relapse in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Dose-intensified CVP induction therapy: Patients receive cyclophosphamide IV and vincristine IV on day 1. Patients also receive oral prednisone on days 1-5 and rituximab IV on days 1 and 8, and high-dose methotrexate IV with leucovorin calcium IV rescue on day 8. Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 and continuing until blood counts recover. Treatment repeats approximately every 14 days for 2 courses.
CNS therapy: Patients receive cytarabine intrathecally (IT) with or without hydrocortisone IT on days 1, 4, and 11 of each induction therapy course. Patients with evidence of CNS involvement by lymphoma continue to receive cytarabine IT twice weekly during any induction therapy treatment delay. Patients who demonstrate CSF clearance receive cytarabine IT once weekly for 4 doses and then once every other week for 4 doses during consolidation therapy. Patients with disease progression during induction therapy or persistent CNS involvement by lymphoma are removed from the study. All other patients proceed to consolidation therapy.
Consolidation therapy: Patients receive rituximab IV on day -4 and high-dose cyclophosphamide IV on days -3, -2, -1, and 0. Patients receive G-CSF SC once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6. Patients then receive rituximab IV once weekly for 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 3 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 3 years.

Enrollment

23 patients

Sex

All

Ages

30 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:
- Classic, sporadic Burkitt's lymphoma
- Burkitt's leukemia (FAB L3 acute lymphoblastic leukemia)
- Atypical Burkitt/Burkitt's-like lymphoma or leukemia, defined by the following criteria:
  - Characteristic morphologic features
  - High proliferative index AND Ki-67 ≥ 85%
Any stage allowed
Newly diagnosed or untreated disease
- Steroids allowed

PATIENT CHARACTERISTICS:

Age

30 and over

Performance status

Not specified

Life expectancy

Not specified

Renal

No known irreversible renal dysfunction that would preclude treatment with high-dose cyclophosphamide

Cardiovascular

No known significant cardiac dysfunction that would preclude treatment with high-dose cyclophosphamide

Other

Not pregnant or nursing
No known HIV positivity
No other malignancy within the past 3 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior chemotherapy for lymphoma
- A maximum of 2 prior doses of intrathecal chemotherapy are allowed

Endocrine therapy

Not specified

Radiotherapy

No prior radiation therapy for lymphoma

Surgery

Prior complete or incomplete surgical resection of lymphoma allowed

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

23 participants in 1 patient group

R-CVP + HiCy

Experimental group

Description:

Protocol intervention consists of two fifteen-day cycles of cyclophosphamide (Cy), vincristine (V), prednisone (P), rituximab (R), with filgrastim support. CNS intervention consists of three days of cytarabine and hydrocortisone and one day of methotrexate (with leucovorin support) for each cycle. After those two cycles, rituximab and high-dose cyclophosphamide (HiCy) will be given.

Treatment: