RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells. It is not yet known if combination chemotherapy plus filgrastim is more effective with or without rituximab in treating non-Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy plus filgrastim with or without rituximab in treating older patients who have non-Hodgkin's lymphoma.

Condition	Treatment or Intervention	Phase
adult diffuse large cell lymphoma adult non-Hodgkin's lymphoma grade 3 follicular lymphoma Mantle Cell Lymphoma	Drug: cyclophosphamide  Drug: doxorubicin  Drug: filgrastim  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: monoclonal antibody therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), and filgrastim (G-CSF) with or without rituximab on event-free survival of elderly patients with intermediate or high-risk non-Hodgkin's lymphoma.
• Compare the complete remission rate, overall survival, and disease-free survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, WHO classification, and International Prognostic Index score. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cyclophosphamide IV, doxorubicin IV, and vincristine IV on day 1; oral prednisone on days 1-5; and filgrastim (G-CSF) subcutaneously on days 1-14. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive cyclophosphamide, doxorubicin, vincristine, prednisone, and G-CSF as in arm I. Patients also receive rituximab IV on day 3 of courses 1-2 and on day 1 of courses 3-6 for a total of 6 doses. Patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 5 years.

Ages Eligible for Study:  65 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed non-Hodgkin's lymphoma (NHL)
• Low- or high-intermediate or high-risk lymphoma of any of the following subtypes:
• Mantle cell lymphoma
• Follicular lymphoma (grade III)
• Diffuse large B-cell lymphoma
• CD20-positive
• No suspected or documented CNS involvement by NHL NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS: Age:

• 65 and over

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 1.75 mg/dL*
• Transaminases less than 2.5 times normal* NOTE: * Unless due to NHL

Renal:

• Creatinine less than 1.7 mg/dL (unless due to NHL)

Cardiovascular:

• No severe cardiac dysfunction
• No New York Heart Association class II-IV heart disease
• LVEF at least 45%

Pulmonary:

• No uncontrolled asthma requiring steroid treatment

Other:

• HIV negative
• No intolerance to exogenous protein administration
• No active, uncontrolled infection
• No uncontrolled allergy requiring steroid treatment
• No other malignancy within the past 5 years except basal cell skin cancer or stage 0 cervical cancer

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior immunotherapy for NHL

Chemotherapy:

• No prior chemotherapy for NHL

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for NHL except local radiotherapy for potential organ dysfunction by localized lymphoma mass or infiltration
• Concurrent local radiotherapy for potential or actual organ dysfunction by localized lymphoma mass or infiltration allowed

Surgery:

• Not specified

Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands; Recruiting
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands; Recruiting
      Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam,  3008 AE,  Netherlands; Recruiting
      Isala Klinieken - locatie Sophia, Zwolle,  8000 GK,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Leyenburg Ziekenhuis, S. Gravenhage,  2545 CH,  Netherlands; Recruiting
      Meander Medisch Centrum, Amersfoort,  3816 CP,  Netherlands; Recruiting
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands; Recruiting
      Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands; Recruiting
      Sint Antonius Ziekenhuis, Nieuwegein,  3435 CM,  Netherlands; Recruiting
      University Medical Center Groningen, Groningen,  9713 EZ,  Netherlands; Recruiting
      University Medical Center Utrecht, Utrecht,  3584 CX,  Netherlands; Recruiting
      Vrije Universiteit Medisch Centrum, Amsterdam,  1081HV,  Netherlands; Recruiting

Study chairs or principal investigators

Pieter Sonneveld, MD, PhD,  Study Chair,  Daniel Den Hoed Cancer Center at Erasmus Medical Center   

Study ID Numbers:  CDR0000069122; CKVO-2000-10; HOVON-46NHL; EU-20130; HOVON-CKVO-2000-10; NCT00028717
Record last reviewed:  January 2002
Last Updated:  April 4, 2005
Record first received:  January 4, 2002
ClinicalTrials.gov Identifier:  NCT00028717
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08