Chemotherapy Followed by Radiation Therapy and Peripheral Stem Cell Transplant Compared With Chemotherapy Plus Interferon Alfa in Treating Patients With Stage III or Stage IV Mantle Cell Lymphoma
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Peripheral stem cell transplant 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 giving more than one drug (combination chemotherapy) with radiation therapy and peripheral stem cell transplant is more effective than chemotherapy followed by interferon alfa in treating mantle cell lymphoma.
PURPOSE: This randomized phase III trial compares how well chemotherapy followed by radiation therapy, chemotherapy, and peripheral stem cell transplant works compared to chemotherapy plus interferon alfa in treating patients who have stage III or stage IV mantle cell lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OBJECTIVES:
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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.
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Compare the overall survival of patients treated with early vs late myeloablative radiochemotherapy and PBSCT.
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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
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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.
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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
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Consolidation: Patients receive 2 additional courses of induction chemotherapy as consolidation (for a total of 8 chemotherapy courses).
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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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically confirmed stage III or IV mantle cell lymphoma
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Previously untreated
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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:
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No impairment of liver function (unless due to lymphoma)
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Transaminases no greater than 3 times normal
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Bilirubin no greater than 2.0 mg/dL
Renal:
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No renal insufficiency
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Creatinine no greater than 2.0 mg/dL
Cardiovascular:
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No manifest heart failure or coronary heart disease
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No severe uncontrolled hypertension
Pulmonary:
- No chronic lung disease with hypoxemia
Other:
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Not pregnant or nursing
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Fertile patients must use effective contraception
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No severe uncontrolled diabetes mellitus
PRIOR CONCURRENT THERAPY:
Biologic therapy:
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No prior interferon
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AZ Sint-Jan | Brugge | Belgium | 8000 | |
| 2 | Ospedale Civile Alessandria | Alessandria | Italy | I-15100 |
Sponsors and Collaborators
- German Low Grade Lymphoma Study Group
- European Organisation for Research and Treatment of Cancer - EORTC
- Gruppo Italiano Studio Linfomi
- Lymphoma Study Association
Investigators
- Study Chair: Wolfgang Hiddemann, MD, PhD, Klinikum der Universitaet Muenchen - Grosshadern Campus
- Study Chair: J. C. Kluin-Nelemans, MD, PhD, University Medical Center Groningen
- Study Chair: Alessandro Levis, MD, Ospedale Civile Alessandria
- Study Chair: Achiel Van Hoof, MD, AZ Sint-Jan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CDR0000068609
- GER-LGLSG-INTERGROUP-20995
- EORTC-20995
- GELA-INTERGROUP-20995
- GISL-INTERGROUP-20995