Combination Study of Revlimid®, Velcade® Dexamethasone and Doxil® (RVDD)for Newly Diagnosed Multiple Myeloma (RVDD)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multi-Institutional Phase I/II Study of Revlimid® (Lenalidomide), Velcade® (Bortezomib), Dexamethasone, and Doxil®, (RVDD) Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma|
- Maximum Tolerated Dose (MTD) of Combination Therapy With VELCADE, Dexamethasone, and Doxil, (RVDD) [ Time Frame: 1 month post treatment ]
Dose Level 1:
15 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4
Dose Level 2:
20 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4
Dose Level 3:
25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 20 mg/m2 Doxil daily on day 4
Dose Level 4:
25 mg Revlimid daily on days 1-14 followed by 7-day rest every 21 days 1.3 mg/m2 Velcade daily on days 1, 4, 8 and 11 20 mg dexamethasone daily on Days 1, 2, 4, 5, 8, 9, 11, 12* and 30 mg/m2 Doxil daily on day 4
- The Percentage of Patients That Achieved Partial or Complete Response to Treatment. [ Time Frame: 24 weeks (8, 21-day cycles) ]
- 50% reduction in the level of serum monoclonal protein for at least two determinations six weeks apart.
- If present, reduction in 24-hour urinary light chain excretion by either, greater than or equal to 90%, or to <200 mg for at least two determinations six weeks apart.
- 50% reduction in the size of soft tissue plasmacytomas (by clinical or radiographic examination) for at least six weeks.
- No increase in size or number of lytic bone lesions (development of compression fracture does not exclude response).
- Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of six weeks.
- <5% plasma cells in the bone marrow on at least two determinations for a minimum of six weeks.
- No increase in the size or number of lytic bone lesions.
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||January 2017|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Experimental: Combination Drug Therapy
Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11, Doxil at indicated doses on day 4, Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels, and Revlimid at indicated doses on days 1-14 in 3-week cycles for 4-8 cycles. To determine the MTD of the combination of Revlimid, Velcade, dexamethasone, and Doxil, four dose levels are planned.
Patients will be treated with Revlimid on days 1-14 in 3-week cycles for 4-8 cycles.
Other Name: RevlimidDrug: Bortezomib
Patients will be treated with Velcade at 1.3 mg/m2 on days 1, 4, 8, and 11
Other Name: VelcadeDrug: Dexamethasone
Patients will be treated with Dexamethasone at 20 mg orally on days of Velcade and the day after for all dose levels.Drug: Doxil
Patients will be treated with Doxil on day 4.
During the Phase I portion of this clinical trial, the doses of Revlimid® and Doxil® will be increased until the best and safest amount (or dose) is identified in combination with Velcade® and Dexamethasone. "Investigational" means that the drug combination is still being studied and that research doctors are trying to find out more about it such as the safest dose to use, the side effects it may cause and how effective the Velcade®, Doxil®, Dexamethasone and Revlimid® investigational combination is for treating newly diagnosed multiple myeloma. In this clinical trial we are looking for the highest dose of the combination that can be given safely and see how well it works as a combination in newly diagnosed patients.
Each of these drugs, Velcade®, Doxil®, Dexamethasone and Revlimid® are approved by the FDA (U.S. Food and Drug Administration). They have not been approved in this combination for use for your type of cancer or any other type of cancer. Velcade® is currently approved by the United States Food and Drug Administration (US FDA) for the treatment of multiple myeloma patients who have received at least one prior therapy. Doxil® has recently been approved by the US FDA for multiple myeloma in combination with Velcade® in patients who have not previously received Velcade® and have received at least one prior therapy. Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Revlimid® is currently approved by the US FDA in combination with dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy.
After the Phase I clinical trial defines the safest doses of Velcade®, Doxil®, Dexamethasone and Revlimid® that can be taken together, the research study will move on to its second portion, a Phase II clinical trial. The Phase II portion of the clinical trial will test the clinical effectiveness of the best dose combination of the four drugs.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00724568
|United States, Georgia|
|Emory University Hospital|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|The University of Chicago Medical Center|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Dana Farber Cancer Institute (and Massachusetts General)|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|University of Michigan Comprehensive Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|United States, Ohio|
|The Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Moshe Talpaz, MD||University of Michigan Cancer Center|