RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, prednisone, and gemcitabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining cyclophosphamide, doxorubicin, vincristine, and prednisone with or without gemcitabine in treating patients who have previously untreated aggressive stage II, stage III, or stage IV non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult diffuse large cell lymphoma anaplastic large cell lymphoma angioimmunoblastic T-cell lymphoma grade 3 follicular lymphoma	Drug: cyclophosphamide  Drug: doxorubicin  Drug: gemcitabine  Drug: prednisone  Drug: vincristine  Procedure: chemotherapy	Phase II

OBJECTIVES: Primary

• Compare the complete response rate (confirmed or unconfirmed) in patients with previously untreated aggressive non-Hodgkin’s lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone with vs without gemcitabine.

Secondary

• Compare the safety profile of these regimens in these patients.
• Compare the feasibility of these regimens, defined as the proportion of courses given as scheduled, in these patients.
• Compare freedom from treatment failure in patients treated with these regimens.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are stratified according to participating center, International Prognostic Index score (0-2 vs 3-5), and histology (B cell vs T cell). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1 and oral or IV prednisone on days 1-5.
• Arm II: Patients receive CHOP chemotherapy as in arm I and gemcitabine IV over 30 minutes on days 1 and 8. In both arms, treatment repeats every 3 weeks for 3 courses in the absence of unacceptable toxicity or progressive disease. Patients achieving partial response or complete or unconfirmed complete response receive an additional 5 courses of therapy (for a total of 8 courses).

Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 76-82 patients (38-41 per treatment arm) will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed aggressive non-Hodgkin’s lymphoma (NHL) of 1 of the following subtypes:
• B large cell (including diffuse, mediastinal, primary effusion, or other subtypes)
• Follicular high-grade
• T peripheral (including nasal type and other subtypes)
• Anaplastic large cell of T or 0 immunophenotype
• Stage II-IV disease
• At least 1 site of measurable disease (e.g., lymph node or lymph node mass)
• No Burkitt’s or lymphoblastic lymphoma
• No primary skin lymphoma
• No CNS involvement by lymphoma

PATIENT CHARACTERISTICS: Age

• 18 to 70

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• WBC > 3,000/mm^3
• Neutrophil count > 1,000/mm^3
• Platelet count > 100,000/mm^3

Hepatic

• Bilirubin < 2.5 times normal (unless due to lymphoma)
• ALT and AST < 2.5 times normal (unless due to lymphoma)

Renal

• Creatinine < 2.0 mg/dL

Cardiovascular

• No severe cardiac disease that would preclude study participation or limit life expectancy

Pulmonary

• No severe pulmonary disease that would preclude study participation or limit life expectancy

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative
• No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No severe neurologic or metabolic disease that would preclude study participation or limit life expectancy
• No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY: Biologic therapy

• No concurrent monoclonal antibodies

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No prior cytotoxic agents
• No prior treatment for NHL
• No other concurrent anticancer therapy
• No other concurrent investigational drugs

Croatia
      University Hospital Rebro, Zagreb,  41000,  Croatia; Recruiting

Study chairs or principal investigators

Igor Aurer, MD, PhD,  University Hospital Rebro   

Study ID Numbers:  CDR0000355123; EORTC-20021
Record last reviewed:  February 2004
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00079261
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-17