Bortezomib After Combination Chemotherapy, Rituximab, and an Autologous Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma

Mantle Cell Lymphoma Clinical Trial

Official title: A Randomized Phase II Trial of Maintenance vs Consolidation Bortezomib Therapy Following Aggressive Chemo-Immunotherapy and Autologous Stem Cell Transplant for Previously Untreated Mantle Cell Lymphoma

Status Active, not recruiting

Clinical Trial Summary

This randomized phase II trial studies how well bortezomib works when given after combination chemotherapy, rituximab, and an autologous stem cell transplant in treating patients with mantle cell lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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. Giving more than one drug (combination chemotherapy) together with an autologous stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving bortezomib after combination chemotherapy, monoclonal antibody therapy, and an autologous stem cell transplant may kill any remaining cancer cells or keep the cancer from coming back.

Clinical Trial Description

Objectives

Primary Objective:

To determine the 18-month progression-free survival (PFS) in patients with previously untreated mantle cell lymphoma who are treated with aggressive chemo-immunotherapy and autologous stem cell transplant followed by randomization to either maintenance or consolidation bortezomib therapy

Secondary Objectives:

• To determine the toxicity profiles of maintenance and consolidation bortezomib by evaluating the number of patients able to complete all maintenance or consolidation therapy

• To determine the complete response rate to intensive chemo-immunotherapy plus maintenance or consolidation bortezomib

• To determine time to progression and overall survival using these two treatment regimens

Correlative/Other Pre-Specified Objectives:

• To determine the importance of p53 mutation or deletion on patient outcome with respect to CR rate, PFS, and OS

• To determine the importance of Ki67, cyclin D1, phosphohistone 3, p27, p21, p16, and PARP p85 expression in pre-treatment tumor biopsies with respect to CR rate, PFS, and OS

• To determine the relationship between proliferation signature and clinical outcome using quantitative real-time RT-PCR

• To evaluate the importance of quantitative cyclin D1 expression and expression of cyclin D1 isoforms in predicting clinical outcome using quantitative real-time RT-PCR

• To evaluate the prognostic significance of microRNAs in mantle cell lymphoma using microRNA arras

• To explore the correlation of selected microRNA polymorphisms with gene target expression with clinical outcomes such as response, PFS, and OS

• To determine changes in gene expression profile from diagnosis to relapse samples to identify genes differentially silenced or over-expressed with disease recurrence

• To determine the importance of early PCR negativity (following Treatment 2) using bcl-1/IgH junction and/or IgH chain gene rearrangement with respect to maintained PFS and the success of maintenance or consolidation therapy to converting patients to PCR negative status

OUTLINE OF INTERVENTIONS:

CHEMOIMMUNOTHERAPY: Patients receive chemoimmunotherapy comprising rituximab* intravenously (IV) over 4-6 hours on day 1, methotrexate (MTX) IV over 4 hours on day 2, cyclophosphamide IV over 2 hours, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 3, and prednisone orally (PO) on days 3-7. Beginning 24 hours after completion of MTX, patients receive leucovorin calcium IV every 6 hours until blood levels of MTX are in a safe range. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily (QD) beginning on day 3 and continuing until blood counts recover. Beginning no sooner than day 22, but no later that day 29 of the first course, patients receive a second course of chemoimmunotherapy as above. Patients with > 15% persistent bone marrow involvement may receive a third course of chemoimmunotherapy. Patients are restaged and those with progressive disease are removed from therapy.

NOTE: *During the first course of chemoimmunotherapy, patients receive rituximab only if the number of circulating mantle cells is =< 10,000/mm^3, otherwise, rituximab is omitted during the first course of chemoimmunotherapy.

HIGH-DOSE CONSOLIDATION CHEMOIMMUNOTHERAPY AND PERIPHERAL BLOOD STEM CELL (PBSC) COLLECTION:

Approximately 4 weeks after completion of chemoimmunotherapy, patients receive high-dose consolidation chemoimmunotherapy comprising cytarabine IV over 2 hours and etoposide phosphate IV continuously on days 1-4, and rituximab IV over 4-6 hours on days 5 and 12 OR 6 and 13. Beginning on day 14 and continuing until completion of PBSC collection, patients receive G-CSF SC QD. Once blood counts recover, patients undergo 1-3 leukapheresis procedures for collection of PBSCs on days 22-25.

HIGH-DOSE CHEMOTHERAPY AND AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Beginning 4-6 weeks after completion of leukapheresis, patients receive carmustine IV over 2 hours on day -6, etoposide phosphate IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous PBSCT on day 0. Patients also receive G-CSF SC QD beginning on day 4 and continuing until blood counts recover.

POST-TRANSPLANTATION IMMUNOTHERAPY: Approximately 5 weeks after autologous PBSCT, patients receive rituximab IV over 4-6 hours once weekly for 2 weeks. Approximately 4 weeks after completion of post-transplantation immunotherapy, patients proceed to maintenance therapy or consolidation therapy with bortezomib as described in the Arms section.

After completion of study treatment, patients are followed every 2 months for 2 years, every 6 months for 3 years, and then annually for 5 years. ;

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma

• NCT number: NCT00310037
• Study type: Interventional
• Source: Alliance for Clinical Trials in Oncology
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 2006