Bendamustine, Wkly Bortezomib, Lenalidomide and Dexamethasone for Multiple Myeloma (BVRD)
The purpose of the study is to determine the safety and efficacy of the use of Bendamustine in combination with a commonly used combination chemotherapy to treat relapsed and refractory multiple myeloma. The study will be conducted in two phases. Participants in phase I will receive 1 of 4 escalating doses of bendamustine. Once the maximum tolerated dose of bendamustine is determined phase II of this trial will begin. Participants in phase II will receive the maximum tolerated dose of bendamustine in combination with standard of care chemotherapy.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label Phase I/II Study of Bendamustine, Weekly Bortezomib, Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma|
- Maximally Tolerated Dose of Bendamustine [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]Primary objective of this phase is to determine the MTD of bendamustine when combined with bortezomib, lenalidomide and dexamethasone in subjects with relapsed and/or refractory multiple myeloma.
- Drug Toxicity [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
toxicity is defined as the inability to complete cycle 1 due to the following: Grade 3 or higher non-hematologic toxicity that are clearly not related to disease progression or intercurrent illness
- nausea, vomiting, diarrhea,
- Grade 3 or 4 venous thromboembolic events
- Grade 4 hematologic toxicity defined as: thrombocytopenia with platelets less than or equal to 10,000 on more than one occasion despite transfusion support
- Survival [ Time Frame: 168 days ] [ Designated as safety issue: Yes ]The secondary objectives of the phase II portion of this study are to identify Median Progression-free survival, Median Overall Survival, Median Time to Next Treatment, and to identify any prognostic features that correlate to improved response.
- Response Rates [ Time Frame: 168 days ] [ Designated as safety issue: Yes ]The primary objective of the phase II portion of this study is to determine the overall response rate (Minor Response (MR), partial response (PR), very good partial response (VGPR), complete response (CR), and stringent complete response (SCR) in patients treated with bendamustine in combination with weekly bortezomib, plus lenalidomide and dexamethasone. ORR will be calculated as the percentage of patients who achieve a MR or better after up to 8 cycles of protocol therapy.
|Study Start Date:||May 2011|
|Estimated Study Completion Date:||May 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Phase I of the study will determine the safest dose of Bendamustine that can be combined with standard chemotherapy. Bendamustine will be given in doses of 25, 50, 75, 100, and 125 mg/m2. The first group of 3 patients to enter the study will receive a 25 mg/m2 dose of Bendamustine. If this dose is found to be safe, the next 3 patients will receive 50 mg/m2. The dose will continue to increase until the maximum tolerated dose (MTD)is found. Once the MTD is found the study will progress to phase II.
The first group of 3 patients to enter the study will receive a 25 mg/m2 dose of Bendamustine. If this dose is found to be safe, the next 3 patients will receive 50 mg/m2. The dose will continue to increase until the highest safe dose of Bendamustine is found. Bendamustine and Bortezomib will be given through a catheter twice a week every 21 days. Dexamethasone and Lenalidomide will be given orally. In general, a cycle of chemotherapy will last 21 days.
Other Name: TreandaDrug: Bortezomib
Bortezomib will be given through a catheter twice a week every 21 days.
Other Name: VelcadeDrug: Lenalidomide
Lenalidomide will be given orally taken as instructed by the physician.
Other Name: RevlimidDrug: Dexamethasone
Dexamethasone will be given orally as instructed by the physician.
Other Name: Steroid
Multiple myeloma is a multi-organ neoplastic disorder caused by the clonal proliferation of plasma cells. It has an incidence of about 4.5/100,000 per year in the U.S., making it the second most common hematologic malignancy. For many years, alkylating agents have been the backbone of treatment. The combination of melphalan and prednisone was, for many years, the standard of care for patients who were not candidates for autologous transplantation. Melphalan continues to be the primary conditioning agent for autologous transplant,and cyclophosphamide has also gained a foothold in the treatment of this disease.
The introduction of novel agents has fundamentally changed the landscape of treating this disease, although the true effects on survival are not yet known. Immunomodulatory agents and proteosome inhibitors, including thalidomide, lenalidomide and bortezomib, have been used in both newly diagnosed and relapsed patients. Currently, there is intense clinical research on the optimal way to combine these novel agents with the traditional backbones of treatment - including alkylators, with one another and, eventually, with the subsequent iterations of these classes of drugs. However, despite the therapeutic excitement surrounding this disease, nearly all patients will relapse, and cure remains an elusive goal for all but a rare handful.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01484626
|Contact: Laura Michaelis, MDemail@example.com|
|Contact: Michelle Deutsch, RNfirstname.lastname@example.org|
|United States, Illinois|
|Loyola Univ Med Cntr - Cardinal Bernardin Cancer Center||Recruiting|
|Maywood, Illinois, United States, 60153|
|Contact: Laura Michaelis, MD 708-327-3216 email@example.com|
|Contact: Michelle Deutsch, RN 708-327-3022 firstname.lastname@example.org|
|Principal Investigator: Laura Michaelis, MD|
|Principal Investigator:||Laura Michaelis, MD||Loyola Univ Med Cntr - Cardinal Bernardin Cancer Cntr|