Trial Information

Phase II Study of Multimodality Therapy in Mantle Cell Lymphoma

OBJECTIVES:

- Determine the toxicities of combination chemotherapy followed by allogeneic or
autologous bone marrow transplantation or peripheral blood stem cell transplantation
and/or interferon and interleukin therapy in patients with refractory or stage III or
IV mantle cell lymphoma.

- Determine the complete response rate in these patients after these treatments.

- Evaluate the prognostic factors in this patient population.

OUTLINE: This is a multicenter study.

Patients receive induction chemotherapy consisting of cyclophosphamide IV, doxorubicin IV,
and teniposide IV over 2 hours on day 1, oral prednisone on days 1-5, vincristine IV and
methotrexate IV over 2 hours on day 21, cytarabine IV over 2 hours every 12 hours for a
total of 2 doses on day 22, and oral leucovorin calcium every 6 hours beginning on day 22
and continuing until methotrexate levels recover. Treatment repeats every 42 days for 2
courses. Patients achieving complete response or partial response receive an additional
course of induction therapy. Patients achieving maximal response following 2 courses of
induction chemotherapy undergo transplantation.

Patients under 50 years with an HLA matched donor undergo allogeneic bone marrow
transplantation (BMT). Patients receive busulfan IV every 6 hours for a total of 14 doses
beginning on day -8 and continuing for 3.5 days. At 24 hours following the last dose of
busulfan, patients receive cyclophosphamide IV over 2 hours daily for 2 days. Patients
receive allogeneic bone marrow infusion on day 0.

Patients under 50 years with no HLA matched donor or patients 50-65 years old undergo
autologous bone marrow or peripheral blood stem cell (PBSC) transplantation. Patients
undergo PBSC mobilization following completion of cyclophosphamide, doxorubicin, and
teniposide portion of induction therapy of course 3. Patients receive cytokines
subcutaneously (SQ) beginning 2 days following chemotherapy and continuing through PBSC
collection. If insufficient stem cells are collected and there is negative bone marrow
involvement, patients undergo bone marrow harvest. Patients receive a conditioning regimen
consisting of busulfan and cyclophosphamide as for allogeneic BMT. Patients receive
autologous bone marrow or PBSC infusion on day 0 and filgrastim (G-CSF) SQ beginning on day
0 and continuing until blood counts recover. Following blood count recovery, patients
receive maintenance therapy consisting of interferon alfa SQ and interleukin-2 SQ daily over
5 consecutive days for 4 weeks. Treatment repeats every 8 weeks for 2 courses.

Patients 65 years or older achieving complete or partial response to induction chemotherapy
receive maintenance therapy as for autologous BMT. Patients achieving partial response may
receive an additional 4th course of induction therapy prior to maintenance therapy.

Patients are followed at 30 days post transplant, every 3 months for 1 year, and then at
least every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 15-48 patients will be accrued for this study over 3 years.