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

NCT ID: NCT00133991

Last Updated: 2018-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31
• Study Completion Date: 2013-08-31

Brief Summary

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.

Detailed 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.

Conditions

Leukemia; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-CVP + HiCy

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.

Group Type: EXPERIMENTAL

Filgrastim

Intervention Type: BIOLOGICAL

5 mcg/kg/day starting on Day 3 after each R-CVP cycle and on Day 6 after HiCy.

Rituximab

Intervention Type: BIOLOGICAL

375 mg/m\^2 on Day 1 and Day 8 of each R-CVP cycle. 375 mg/m\^2 on Day -4 of HiCy and weekly for four weeks after HiCy.

Cyclophosphamide

Intervention Type: DRUG

1500 mg/m\^2 on Day 1 of each R-CVP cycle. 50 mg/kg/day on Days -3, -2, -1, and 0 of HiCy.

Cytarabine

Intervention Type: DRUG

100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.

Methotrexate

Intervention Type: DRUG

3 g/m\^2 on Day 8 of each cycle of R-CVP.

Prednisone

Intervention Type: DRUG

100 mg on Days 1-5 of each cycle of R-CVP.

Hydrocortisone

Intervention Type: DRUG

50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.

Vincristine

Intervention Type: DRUG

1.4 mg/m\^2 on Day 1 of each cycle of R-CVP.

Leucovorin

Intervention Type: DRUG

25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.

Interventions

Filgrastim

5 mcg/kg/day starting on Day 3 after each R-CVP cycle and on Day 6 after HiCy.

Intervention Type: BIOLOGICAL

Rituximab

375 mg/m\^2 on Day 1 and Day 8 of each R-CVP cycle. 375 mg/m\^2 on Day -4 of HiCy and weekly for four weeks after HiCy.

Intervention Type: BIOLOGICAL

Cyclophosphamide

1500 mg/m\^2 on Day 1 of each R-CVP cycle. 50 mg/kg/day on Days -3, -2, -1, and 0 of HiCy.

Intervention Type: DRUG

Cytarabine

100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.

Intervention Type: DRUG

Methotrexate

3 g/m\^2 on Day 8 of each cycle of R-CVP.

Intervention Type: DRUG

Prednisone

100 mg on Days 1-5 of each cycle of R-CVP.

Intervention Type: DRUG

Hydrocortisone

50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.

Intervention Type: DRUG

Vincristine

1.4 mg/m\^2 on Day 1 of each cycle of R-CVP.

Intervention Type: DRUG

Leucovorin

25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.

Intervention Type: DRUG

Other Intervention Names

Neupogen; G-CSF; Rituxan; Cytoxan; Cy; CTX; HiCy; Ara-C; MTX; Deltasone; Oncovin; Folinic acid

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yvette L. Kasamon, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Drexel University College of Medicine - Center City Hahnemann Campus

Philadelphia, Pennsylvania, United States

Countries

United States

References

Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolanos-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. doi: 10.3109/10428194.2012.715346. Epub 2012 Aug 17.

Reference Type: RESULT

PMID: 22835045 (View on PubMed)

Other Identifiers

P50CA096888

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NA_00035765

Identifier Type: OTHER

Identifier Source: secondary_id

J0409

Identifier Type: -

Identifier Source: org_study_id