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

Lymphoma Clinical Trial

Official title:

Phase II Study of Intensified CVP, Rituximab, and High Dose Cyclophosphamide for Adult Burkitt or Burkitt-Like Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00133991
• Other study ID #: J0409
• Secondary ID: P50CA096888P30CA
• Status: Completed
• Phase: Phase 2
• Start date: July 2005
• Est. completion date: August 2013

Study information

• Verified date: September 2018
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 2013
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Burkitt Lymphoma
• Leukemia
• Lymphoma

Intervention

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

Drug:
• 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.
• Cytarabine
100 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
• Methotrexate
3 g/m^2 on Day 8 of each cycle of R-CVP.
• Prednisone
100 mg on Days 1-5 of each cycle of R-CVP.
• Hydrocortisone
50 mg intrathecal on Days 1, 4, and 11 of each cycle of R-CVP.
• Vincristine
1.4 mg/m^2 on Day 1 of each cycle of R-CVP.
• Leucovorin
25 mg four times daily after methotrexate administration. Dosing continues until adequate methotrexate levels are reached.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Drexel University College of Medicine - Center City Hahnemann Campus	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypica — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Number of participants who have a complete or partial remission (2007 International Working Group criteria).	Up to 3 months
Primary	Overall Survival	Percentage of participants alive at 1 year and at 3 years.	1 year and 3 years
Primary	Event-free Survival	Percentage of participants alive without relapse at 1 year and 3 years.	1 year and 3 years
Primary	Percentage of Participants Experiencing Grade 3-5 Toxicity	Percentage of participants experiencing at least one grade 3-5 adverse event (by CTCAE 3.0 criteria).	Up to 2 years
Secondary	Relapse Pattern	Percentage of participants experiencing central nervous system (CNS) and systemic relapse.	Up to 6 months