RATIONALE: Colony-stimulating factors such as pegfilgrastim may increase the number of immune system cells found in bone marrow or peripheral blood and may be effective in preventing or controlling neutropenia caused by chemotherapy.

PURPOSE: Randomized phase II trial to compare the effectiveness of two pegfilgrastim regimens in treating neutropenia after chemotherapy in patients who have mantle cell or diffuse large B-cell non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult diffuse large cell lymphoma adult non-Hodgkin's lymphoma Mantle Cell Lymphoma Neutropenia	Drug: cyclophosphamide  Drug: doxorubicin  Drug: pegfilgrastim  Drug: prednisone  Drug: rituximab  Drug: vincristine  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: hematologic toxicity attenuation  Procedure: monoclonal antibody therapy  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the safety and efficacy, as measured by the duration of grade 4 neutropenia, of two different schedules of pegfilgrastim administered 4 hours vs 24 hours after cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP) in patients with stage III or IV or bulky stage II mantle cell or diffuse large B-cell non-Hodgkin's lymphoma .
• Compare response rates in patients treated with these regimens.
• Compare the number of patients who receive all planned doses of this chemotherapy regimen on time when treated with two different schedules of pegfilgrastim.
• Compare the hematologic and nonhematologic toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to lymphoma type (mantle cell vs diffuse large B-cell). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive R-CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, vincristine IV, and rituximab IV on day 1 and oral prednisone on days 1-5. Patients also receive pegfilgrastim subcutaneously (SC) on day 1 (within 4 hours after completion of R-CHOP) and placebo SC on day 2 (within 24 hours after completion of R-CHOP).
• Arm II: Patients receive R-CHOP as in arm I. Patients also receive placebo SC on day 1 (within 4 hours after completion of R-CHOP) and pegfilgrastim SC on day 2 (within 24 hours after completion of R-CHOP). In both arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 16-90 patients (8-45 per treatment arm) will be accrued for this study within 6-20 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histological confirmation of 1 of the following non-Hodgkin's lymphomas:
• Mantle cell lymphoma
• CD5 positive and CD23 negative
• Diffuse large B-cell lymphoma, according to the REAL classification
• International Prognostic Index score 0-2
• Measurable or evaluable disease
• Ann Arbor stage III or IV or bulky stage II disease
• No Burkitt's or B-lymphoblastic lymphoma
• No premalignant myeloid conditions or any malignancy with myeloid characteristics (e.g., myelodysplastic syndromes or acute or chronic myelogenous leukemia)
• No T-cell lymphoma or history of indolent lymphoma
• No CNS involvement

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 75,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic

• AST and ALT less than 3 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 50 mL/min

Cardiovascular

• No history of impaired cardiac status
• No severe heart disease
• No cardiomyopathy
• No congestive heart failure
• LVEF at least 50% at rest by MUGA or echocardiogram

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation
• HIV negative
• No active infection requiring treatment with systemic (IV or oral) anti-infectives (antibiotic, antifungal, or antiviral) within 72 hours of study therapy
• No other malignancy within the past 5 years except surgically cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No neurological contraindication to vincristine (e.g., peripheral neuropathy)
• No known sensitivity to E. coli-derived drug products (e.g., filgrastim [G-CSF], Humulin® insulin, asparaginase, somatotropin, or interferon alfa)
• No psychiatric, addictive, or other disorder that would preclude study compliance or giving informed consent

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior bone marrow or stem cell transplantation
• No prior pegfilgrastim
• No other concurrent hematopoietic growth factors, except epoetin alfa for anemia
• No concurrent WBC transfusions

Chemotherapy

• Not specified

Endocrine therapy

• No other concurrent corticosteroids, except any of the following:
• Protocol-specific prednisone
• Topical or inhaled steroids
• Premedication for chemotherapy
• Treatment for an adverse event

Radiotherapy

• No concurrent radiotherapy

Surgery

• More than 2 weeks since prior major surgery

Other

• No prior therapy for malignancy
• At least 30 days since prior participation in an investigational device or drug study
• No concurrent enrollment in another investigational device or drug study
• No other concurrent investigational agents

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-7059,  United States; Recruiting

Study chairs or principal investigators

Peter Rosen, MD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000319032; UCLA-0212095; AMGEN-20020134; NCT00066833
Record last reviewed:  July 2003
Last Updated:  December 9, 2004
Record first received:  August 6, 2003
ClinicalTrials.gov Identifier:  NCT00066833
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08