Clinical trial NCT01412879
Conditions: Lymphoma
Keywords: contiguous stage II mantle cell lymphoma noncontiguous stage II mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma
Sponsor: SWOG Cancer Research Network
Start date: 2011-11-01; Completion date: 2021-03-01
Enrollment: 53 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy also work in different ways to kill more cancer cells or stop them from growing. It is not yet known whether rituximab is more effective with combination chemotherapy or bendamustine hydrochloride in treating patients with mantle cell lymphoma undergoing peripheral blood stem cell transplantation.

PURPOSE: This randomized phase II trial studies how well giving rituximab together with combination chemotherapy or bendamustine hydrochloride followed by consolidation chemotherapy and peripheral blood stem cell transplantation works in treating older patients with previously untreated mantle cell lymphoma.

Detailed description:
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.

Arms: arm 1: Course 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 then undergo stem cell collection after completion of course 2. Patients undergo stem cell collection after completion of course 2. arm 2: 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. 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.
Interventions: intervention 1: rituximab intervention 2: bendamustine hydrochloride intervention 3: cyclophosphamide intervention 4: cytarabine intervention 5: dexamethasone intervention 6: doxorubicin hydrochloride intervention 7: leucovorin calcium intervention 8: methotrexate intervention 9: vincristine sulfate
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV intervention 5: Given PO or IV intervention 6: Given IV intervention 7: Given PO or IV intervention 8: Given IV intervention 9: Given IV

Protocol documents: