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. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Interferon alfa may interfere with the growth of cancer cells. It is not yet known whether chemotherapy combined with radiation therapy and peripheral stem cell transplantation is more effective than chemotherapy followed by interferon alfa in treating mantle cell lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by radiation therapy, chemotherapy, and peripheral stem cell transplantation with that of chemotherapy plus interferon alfa in treating patients who have stage III or stage IV mantle cell lymphoma.

Condition	Treatment or Intervention	Phase
stage III mantle cell lymphoma stage IV mantle cell lymphoma	Drug: carmustine  Drug: cyclophosphamide  Drug: cytarabine  Drug: dexamethasone  Drug: etoposide  Drug: filgrastim  Drug: interferon alfa  Drug: melphalan  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: high-dose chemotherapy  Procedure: interferon therapy  Procedure: peripheral blood stem cell transplantation  Procedure: radiation therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the disease-free survival of patients with previously untreated advanced mantle cell lymphoma treated with intensified chemotherapy followed by myeloablative radiochemotherapy and peripheral blood stem cell transplantation (PBSCT) vs standard therapy and interferon alfa maintenance.
• Compare the overall survival of patients treated with early vs late myeloablative radiochemotherapy and PBSCT.
• Compare disease-free survival and overall survival of patients treated with this regimen vs historic controls of similar cases.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk factors (ECOG performance status greater than 1, LDH serum level above normal, and/or extranodal lymphoma involvement) and participating center. Patients are randomized to 1 of 2 treatment arms.

• Induction: All patients receive 4 courses of cytoreductive chemotherapy comprising an anthracycline-containing combination. Patients not achieving complete remission after 4 courses receive 2 additional courses of induction chemotherapy. Patients without at least a partial response after 6 courses discontinue treatment; those with at least a partial response proceed to arm I or II.

Arm I

• Consolidation: Patients achieving complete or partial remission after 4-6 courses of induction therapy begin intensified chemotherapy within 6 weeks. Patients receive oral dexamethasone daily on days 1-10, carmustine IV on day 2, melphalan IV on day 3, etoposide IV daily and cytarabine IV twice a day on days 4-7. Patients also receive filgrastim (G-CSF) beginning on day 11 and continuing until peripheral blood stem cells (PBSC) are harvested.
• Within 4-6 weeks after PBSC harvest, patients undergo myeloablative radiochemotherapy comprising radiotherapy on days -6 to -4 and cyclophosphamide IV on days -3 to -2. Patients then undergo PBSC transplantation on day 0.

Arm II

• Consolidation: Patients receive 2 additional courses of induction chemotherapy as consolidation (for a total of 8 chemotherapy courses).
• Maintenance: Within 4 weeks after arm II consolidation, patients receive interferon alfa subcutaneously (SC) 3 days a week in the absence of unacceptable toxicity or disease progression or relapse. Patients who experience first relapse or progression during maintenance therapy may receive intensified chemotherapy as in arm I. Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 210 patients will be accrued for this study within 5 years.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III or IV mantle cell lymphoma
• Previously untreated
• Not qualified for primary potentially curative radiotherapy

PATIENT CHARACTERISTICS: Age:

• 18 to 65 years

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No impairment of liver function (unless due to lymphoma)
• Transaminases no greater than 3 times normal
• Bilirubin no greater than 2.0 mg/dL

Renal:

• No renal insufficiency
• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No manifest heart failure or coronary heart disease
• No severe uncontrolled hypertension

Pulmonary:

• No chronic lung disease with hypoxemia

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No severe uncontrolled diabetes mellitus

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior interferon
• No prior organ, bone marrow, or peripheral blood stem cell transplantation

Chemotherapy:

• No prior cytostatic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Belgium
      AZ Sint-Jan, Brugge,  8000,  Belgium; Recruiting
Italy
      Ospedale Civile Alessandria, Alessandria,  I-15100,  Italy; Recruiting

Study chairs or principal investigators

Wolfgang Hiddemann, MD, PhD,  Study Chair,  Klinikum Grosshadern der Ludwig-Maximilians Universitaet Muenchen   
J. C. Kluin-Nelemans, MD, PhD,  Study Chair,  University Medical Center Groningen   
Alessandro Levis, MD,  Study Chair,  Ospedale Civile Alessandria   
Achiel Van Hoof, MD,  Study Chair,  AZ Sint-Jan   

Study ID Numbers:  CDR0000068609; GER-LGLSG-INTERGROUP-20995; EORTC-20995; GELA-INTERGROUP-20995; GISL-INTERGROUP-20995; NCT00016887
Record last reviewed:  September 2003
Last Updated:  April 4, 2005
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00016887
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08