EPOCH-R Chemotherapy Plus Bortezomib to Treat Mantle Cell Lymphoma
This study will evaluate the effectiveness of EPOCH-R chemotherapy plus bortezomib for treating mantle cell lymphoma, a cancer of white blood cells called lymphocytes. EPOCH-R consists of the drugs prednisone, etoposide, doxorubicin and vincristine, with the addition of a new drug called rituximab. In a recent study of patients with newly diagnosed mantle cell lymphoma, 92 percent had a complete remission of their disease after treatment with EPOCH-R. This study will test whether adding bortezomib as "maintenance therapy" once chemotherapy is finished will lengthen the time before the disease relapses and improve the overall cure rate.
Patients 18 years of age and older with mantle cell lymphoma may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, MUGA or echocardiogram, imaging studies and biopsy to determine the extent of disease, and possible colonoscopy.
Participants undergo treatment in three parts, as follows:
- Part 1: Bortezomib alone: Patients receive 4 doses of bortezomib over 3 weeks. The drug is injected into a vein over about 30 seconds.
- Part 2: EPOCH-R chemotherapy plus bortezomib: This phase of treatment begins 3 to 4 weeks after completing Part 1. Treatment is given on an outpatient basis in six 3-week cycles, with all drugs administered over the first 5 days of each cycle. Patients take prednisone by mouth on days 1 to 5 and etoposide, doxorubicin, and vincristine as a 96-hour infusion through a vein over days 1 to 5. The infused drugs are delivered through a lightweight, portable infusion pump. Rituximab is given by vein over several hours on day 1 immediately before the chemotherapy infusion begins. Bortezomib is given by vein over 30 seconds on day 1 before the rituximab and again on day 4. Cyclophosphamide is given by vein over about 15 minutes on day 5 immediately after the chemotherapy infusion is completed. Patients are taught how to self inject G-CSF, a drug that helps boost white cell counts after chemotherapy. They inject the drug under the skin (like an insulin shot) for 10 days of each cycle beginning day 6. Patients also take an antibiotic to help prevent infection during chemotherapy.
- Part 3: Bortezomib alone: After completing EPOCH-R-B therapy, patients are randomly assigned to receive or not to receive bortezomib alone. The drug is given in 2 doses over 5 days, with a break of 16 days before the next dose. These 3-week cycles continue for up to 18 months or until the disease comes back or worsens. Patients who are assigned to the group that does not receive bortezomib will be offered the drug if their disease relapses.
During therapy, patients have tests performed on their bone marrow, tumor tissue, blood or other fluids to look at different genes and proteins that may be involved in the development of their lymphoma or the reaction of the immune system. A tissue biopsy is done before treatment begins and a day after treatment starts. Disease progress is followed with CT scans and blood tests. When treatment is completed, patients whose cancer has disappeared are scheduled for periodic follow-up examinations and tests. Those whose disease remains or recurs may be offered participation in another protocol if an appropriate one is available or are returned to the care of their local physician.
Lymphoma, Mantle Cell
Other: clinical observation
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Phase II Study of Dose-Adjusted EPOCH-Rituximab-Bortezomib (EPOCH-R-B) Induction Followed by Bortezomib Maintenance Versus Observation in Untreated Mantle Cell Lymphoma With Microarray Profiling and Proteomics|
- Progression-free survival and overall survival 5 years after completion of study treatment [ Designated as safety issue: No ]
- Response at the end of dose-adjusted induction therapy [ Designated as safety issue: No ]
- Response and toxicity at the end of maintenance therapy [ Designated as safety issue: Yes ]
- Response and progression-free survival of bortezomib at disease progression in the observation treatment arm 5 years after completion of study treatment [ Designated as safety issue: No ]
- Time to non-protocol treatment in the maintenance and observation treatment arms 5 years after completion of study treatment [ Designated as safety issue: No ]
- Correlation of microarray and proteomic findings with clinical outcomes as measured by cDNA microarray 5 years after completion of study treatment [ Designated as safety issue: No ]
|Study Start Date:||June 2005|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Beginning 8-12 weeks after the completion of dose-adjusted induction therapy, patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 8 weeks for up to 18 months in the absence of disease progression or unacceptable toxicity.
Active Comparator: Arm II
Patients undergo observation only. Patients with disease progression receive bortezomib as in arm I. Treatment repeats every 4 weeks for up to 18 months.
Other: clinical observation
Mantle cell lymphoma (MCL) presents a clinical challenge because it is aggressive and incurable with chemotherapy. Therefore novel treatment approaches are needed.
MCL has overexpression of NF-kappa B (NF-kappa B), a transcription factor that affects cell growth and survival, and cyclin D1 that affects cell cycle and growth. These proteins appear to be involved in the pathogenesis of MCL.
Bortezomib, a proteasome inhibitor that inhibits NF-kappa B and cyclin D1, has demonstrated activity in patients with relapsed or refractory MCL.
Dose-adjusted-EPOCH-R has excellent activity in MCL, with a complete response (CR) rate of 92%, but patients eventually relapse.
Determine the PFS and OS of DA-EPOCH-RB followed by bortezomib maintenance versus observation.
Diagnosis of mantle cell lymphoma.
No prior treatment except for local radiation or a short course of steroids for control of symptoms,
Age greater than or equal to 18 years old.
Adequate major organ function unless impairment is due to lymphoma.
To assess the clinical activity and biological effects of bortezomib, patients will initially receive one cycle of bortezomib alone with sequential tumor biopsies for microarray analysis.
All patients will then receive Dose-adjusted (DA)-EPOCH-RB for 6 cycles, and if they have at least a PR, this will be followed by randomization to either immediate bortezomib maintenance x 18 months, or to observation, followed by bortezomib if progression occurs. This study has as a primary goal, to describe progression free survival (PFS) and overall survival of early bortezomib maintenance versus observation following induction with bortezomib followed by DA-EPOCH-RB. Important secondary goals are to assess response and toxicity to bortezomib alone or DA-EPOCH-RB, to evaluate time to progression after receiving bortezomib following progression on an observation arm, and to assess the biological effects of bortezomib on untreated MCL.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00114738
|Contact: Margaret Shovlin, R.N.||(301) firstname.lastname@example.org|
|Contact: Wyndham H Wilson, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Wyndham H Wilson, M.D.||National Cancer Institute (NCI)|