Trial Information

Treatment of Mantle Cell Lymphomas at Advanced Stages: Prospective Randomized Comparison of Myeloablative Radiochemotherapy Followed by Blood Stem Cell Transplantation Versus Maintenance With Interferon Alpha in First Remission After Initial Cytoreductive Chemotherapy With an Anthracycline Containing Combination

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.