Bortezomib After Combination Chemotherapy, Rituximab, and an Autologous Stem Cell Transplant in Treating Patients With Mantle Cell Lymphoma
- Registration Number
- NCT00310037
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 151
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A maintenance therapy bortezomib Patients receive bortezomib 1.6 mg/m\^2 IV on days 1, 8, 15, and 22 once daily for 4 weeks. There will be a 4 week rest period. One cycle is a total of 8 weeks. A total of 10 cycles of bortezomib will be given in the absence of disease progression or unacceptable toxicity. Arm B consolidation therapy bortezomib Patients receive bortezomib 1.3 mg/m\^2 IV on days 1, 4, 8, and 11 once daily for 3 weeks. One cycle is a total of 3 weeks. A total of 4 cycles of bortezomib will be given in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free Survival Rate at 18 Months At 18 months Progression free survival (PFS) rate at 18 months was defined as the proportion of patients that were alive and progression-free 18 months after registration into the study. The Kaplan-Meier method of 18 month progression-free survival was calculated..
- Secondary Outcome Measures
Name Time Method Number of Participants With Complete Response Intensive Chemo-immunotherapy Plus Maintenance or Consolidation Bortezomib Up to 10 years Complete response is:
* Complete disappearance of all detectable clinical and radiographic evidence of target lesions and disappearance of all disease-related symptoms if present prior to therapy and normalization of biochemical abnormalities definitely assignable to NHL
* All lymph nodes and nodal masses must have regressed to normal size (\<= 1.5 cm in the greatest transverse diameter (GTD) for nodes \> 1.5 cm prior to therapy) or \<= 1 cm for nodes that were 1.1-1.5 cm in the GTD prior to therapy or by more than 75% in the sum of the products of the GTD
* The spleen, if enlarged before therapy, must have regressed in size and must not be palpable on physical examination. Any macroscopic nodules in any organs detectable on imaging studies should no longer be present. Other organs enlarged prior to therapy due to involvement of lymphoma must have decreased in size
* If bone marrow was involved by lymphoma prior to treatment, infiltrate must be cleared on repeat bone marrow aspirateOverall Survival Up to 10 years Overall Survival (OS) was measured from the date of study entry to date of death due to any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method.
Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment. Duration of treatment (up to approximately 2 years) The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.
Related Research Topics
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Trial Locations
- Locations (48)
Graham Hospital
🇺🇸Canton, Illinois, United States
Illinois CancerCare - Eureka
🇺🇸Eureka, Illinois, United States
Illinois CancerCare - Canton
🇺🇸Canton, Illinois, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Eureka Community Hospital
🇺🇸Eureka, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Dana-Farber/Brigham and Women's Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Illinois CancerCare - Carthage
🇺🇸Carthage, Illinois, United States
Illinois CancerCare - Bloomington
🇺🇸Bloomington, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Galesburg Clinic, PC
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare - Macomb
🇺🇸Macomb, Illinois, United States
McDonough District Hospital
🇺🇸Macomb, Illinois, United States
Illinois CancerCare - Galesburg
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare - Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Illinois CancerCare - Princeton
🇺🇸Princeton, Illinois, United States
Illinois CancerCare - Peru
🇺🇸Peru, Illinois, United States
BroMenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Illinois CancerCare - Community Cancer Center
🇺🇸Normal, Illinois, United States
Community Hospital of Ottawa
🇺🇸Ottawa, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸Ottawa, Illinois, United States
Illinois CancerCare - Pekin
🇺🇸Pekin, Illinois, United States
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Monter Cancer Center of the North Shore-LIJ Health System
🇺🇸Lake Success, New York, United States
Don Monti Comprehensive Cancer Center at North Shore University Hospital
🇺🇸Manhasset, New York, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸Winston-Salem, North Carolina, United States
UCSF Helen Diller Family Comprehensive Cancer Center
🇺🇸San Francisco, California, United States
Long Island Jewish Medical Center
🇺🇸New Hyde Park, New York, United States
St. Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare - Havana
🇺🇸Havana, Illinois, United States
Illinois CancerCare - Monmouth
🇺🇸Monmouth, Illinois, United States
OSF Holy Family Medical Center
🇺🇸Monmouth, Illinois, United States
Community Cancer Center
🇺🇸Normal, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸Peoria, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸Peoria, Illinois, United States
Illinois CancerCare - Spring Valley
🇺🇸Spring Valley, Illinois, United States
Illinois Valley Community Hospital
🇺🇸Peru, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸Saint Louis, Missouri, United States
CCOP - North Shore University Hospital
🇺🇸Manhasset, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States