Trial Information

A Randomized Phase II Trial of R-HCVAD/MTX/ARA-C Induction Followed by Consolidation With an Autologous Stem Cell Transplant Vs. R-Bendamustine Induction Followed by Consolidation With an Autologous Stem Cell Transplant for Patients ≤ 65 Years of Age With Previously Untreated Mantle Cell Lymphoma

OBJECTIVES:

- To estimate the 2-year progression-free survival (PFS) of patients with newly diagnosed
mantle cell lymphoma (MCL) treated with rituximab, cyclophosphamide, doxorubicin
hydrochloride, vincristine sulfate, dexamethasone (RHCVAD), methotrexate and cytarabine
(MTX/Ara-C), and autologous stem cell transplant (ASCT) or rituximab and bendamustine
(R-bendamustine) and autologous stem cell transplant and to select a regimen for
further development.

- To assess the response rate and overall survival of patients with newly diagnosed MCL
treated with R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine and ASCT.

- To assess the toxicity and tolerability of R-HCVAD/MTX/Ara-C and ASCT or R-bendamustine
and ASCT in patients with newly diagnosed MCL.

- To determine the prognostic value of quantitative minimal-residual disease (MRD)
monitoring in the peripheral blood of MCL patients after induction therapy and serially
after high-dose chemotherapy and ASCT on treatment outcome.

- To bank diagnostic tissue sections for future translational research studies.

OUTLINE: This is a multicenter study. Patients are stratified according to risk
classification by Mantle Cell Lymphoma International prognostic Index (MIPI) score (low risk
vs intermediate/high risk). Patients are randomized to 1 of 2 treatment arms.

- Arm I (induction therapy):

- Courses 1 and 3: Patients receive induction therapy comprising rituximab IV on day
1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin
hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and
12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15.
Patients with responsive disease after course 1 proceed to course 2.

- Course 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22
hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and
leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection
after completion of course 2.

- Each course is 21 days long and continues in the absence of disease progression or
unacceptable toxicity.

- Arm II (induction therapy):

- Course 1-6: Patients receive rituximab IV on day 1 and bendamustine hydrochloride
IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 courses in
the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks
later, patients with responsive disease receive 2 additional courses of treatment.

- Stem cell mobilization: Beginning within 8 weeks, patients receive rituximab IV
and cyclophosphamide IV over 1 hour on day 1. Patients then undergo stem cell
collection about 26 days later.

Consolidation therapy: Patients receive one of the following preparative regimens.

- BCV* chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4
hours on day -4; and cyclophosphamide IV over 1 hour on day -2.

- BEAM* chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1
hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and
melphalan IV on day -1.

- TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)** twice
daily on days -8 to -5. Patients also receive etoposide IV on day -4 and
cyclophosphamide IV over 1 hour on day -2.

- NOTE: * Patients 61 years of age or older receive either BCV or BEAM.

- NOTE: * *TBI may not be used for patients 61 years of age and older. Stem cell
transplantation: Patients then undergo autologous peripheral blood stem cell
transplantation on day 0.

After completion of study treatment, patients are followed up every 3 months for 1 year,
every 6 months for 2 years, and then annually for up to 8 years from registration.