RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known if chlorambucil is more effective than radiation therapy in treating follicular lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of chlorambucil with that of radiation therapy in treating patients who have stage III or stage IV follicular lymphoma that has not been previously treated.

Condition	Treatment or Intervention	Phase
stage III grade 1 follicular lymphoma stage III grade 2 follicular lymphoma stage III grade 3 follicular lymphoma stage IV grade 1 follicular lymphoma stage IV grade 2 follicular lymphoma stage IV grade 3 follicular lymphoma	Drug: chlorambucil  Procedure: chemotherapy  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the effect of chlorambucil vs involved-field radiotherapy on progression-free survival of patients with previously untreated stage III or IV follicular lymphoma.
• Compare the complete and partial remission rates and overall survival of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral chlorambucil on days 1-5. Treatment repeats every 4 weeks for 6-8 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients undergo radiotherapy on days 1 and 3 (and days 15 and 17 for split course). Quality of life is assessed at baseline, prior to course 3, 6, and 8 (arm I), and then at 4-6 weeks after study.

Patients are followed at 4-6 weeks, 3-4 months (arm I), 3 months and 6 months (arm II), 11, 12, 15, 18, and 21 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 444 patients (222 per treatment arm) will be accrued for this study within 4 years.

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

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of follicular lymphoma
• Stage III or IV disease
• Grades I, II, or III
• Previously untreated disease
• Nodal and extranodal sites
• Bidimensionally measurable disease by physical examination or diagnostic imaging
• No CNS or orbital non-Hodgkin's lymphoma localization

PATIENT CHARACTERISTICS: Age:

• 18 and over (for patients at EORTC centers)
• 65 and over (for patients at HOVON centers)

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 4,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 6.0 g/dL

Hepatic:

• Not specified

Renal:

• Not specified

Cardiovascular:

• No severe cardiac disease that would preclude study treatment

Pulmonary:

• No severe pulmonary disease that would preclude study treatment

Other:

• HIV negative
• No severe neurologic, psychiatric, or metabolic disease that would preclude study treatment
• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent systemic corticosteroids, including dexamethasone for nausea and vomiting palliation (inhalation and topical corticosteroids allowed)

Radiotherapy:

• No concurrent elective radiotherapy to an adjacent negative lymph node

Surgery:

• Not specified

Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
Netherlands
      Academisch Ziekenhuis Groningen, Groningen,  9713 EZ,  Netherlands
      Akademisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Antoni van Leeuwenhoek Hospital, Amsterdam,  1066 CX,  Netherlands
      Daniel Den Hoed Cancer Center at Erasmus University Medical Center, Rotterdam,  3075 EA,  Netherlands
      Leiden University Medical Center, Leiden,  2300 RC,  Netherlands
      Maastro Clinic, HEERLEN,  NL-6401 PC,  Netherlands
      Medisch Spectrum Twente, ENSCHEDE,  7500 KA,  Netherlands
      Radiotherapeutisch Instituut Limburg-Maastricht, Maastricht,  NL-6229 ET,  Netherlands
      Vrije Universiteit Medisch Centrum, Amsterdam,  1081HV,  Netherlands

Study chairs or principal investigators

Rick L. M. Haas, MD,  Antoni van Leeuwenhoek Hospital   
T. Girinsky, MD,  Institut Gustave Roussy   

Study ID Numbers:  CDR0000069120; CKVO-2001-01; HOVON-47NHL; EU-20131; HOVON-CKTO-2001-01; EORTC-20013
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  January 4, 2002
ClinicalTrials.gov Identifier:  NCT00028691
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08