Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Multiple Myeloma (CarBiRD)
|Multiple Myeloma||Drug: carfilzomib Drug: Dexamethasone Drug: Clarithromycin Drug: Lenalidomide||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Sequential Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD] Therapy for Subjects With Newly Diagnosed Multiple Myeloma|
- Response to Car-BiRD Treatment. [ Time Frame: From baseline to best response, up to 116 weeks. ]
The best response for all patients who had at least one dose of drug was measured.
Stringent Complete Response (sCR), Complete Remission(CR), Very Good Partial Remission(VGPR), Partial Remission (PR), Progressive Disease (PD), Stable Disease (SD).
The response is evaluated based on the IMWG criteria.
- Event Free Survival [ Time Frame: From date of study enrollment until the date of removal of study due to progression of disease, toxicity or withdrawal of consent, up to 1222 days. ]an event is defined by coming off protocol for any reason, including progression of disease, lack of disease response, regimen intolerability, withdrawal of consent or death.
- MRD Negativity Following CarBiRD Regimen [ Time Frame: From start of study up to Revlimid Maintenance Cycle 4. ]
Minimal Residual Disease (MRD) was assessed for all participants as soon as they achieved CR/sCR, regardless of what phase they were on.
MRD negativity is defined as the complete absence of plasma cells on bone marrow biopsy.
MRD positivity is defined as the presence of residual plasma cells (<5%) on bone marrow biopsy.
The IMWG criteria were used to determine CR and sCR.
- Progression Free Survival [ Time Frame: From start of study drug until first incidence of progression, up to 1222 days. ]Progression was defined using the IMWG criteria.
- Stem Cells Collection [ Time Frame: At the end of the Car Phase, prior to the start of the BiRD Phase, on average after 162 days. ]At the end of the Car Phase, all participants underwent stem cell collection.
|Actual Study Start Date:||March 2012|
|Estimated Study Completion Date:||March 2022|
|Primary Completion Date:||June 7, 2016 (Final data collection date for primary outcome measure)|
Experimental: Car-BiRD Therapy
Carfilzomib, Clarithromycin (Biaxin®), Lenalidomide (Revlimid®), and Dexamethasone (Decadron®) [Car-BiRD]
45 mg/m2 IV on days 1, 2, 8, 9, 15 and 16 of each 28 day cycles.Drug: Dexamethasone
20 mg orally on days 1, 2, 8, 9, 15 and 16 of a 28 day cycle, while receiving carfilzomib.
Other Name: DECADRON®Drug: Clarithromycin
500 mg twice a day for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.
Other Name: BiaxinDrug: Lenalidomide
25 mg orally days 1-21 for each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.
Other Name: RevlimidDrug: Dexamethasone
40 mg orally on days 1, 8, 15 and 22 of each 28 day cycle of BiRD treatment. BiRD begins after carfilzomib treatment has been completed.Drug: Lenalidomide
10 mg orally on days 1-21 or each 28 day cycle of maintenance. Maintenance begins after BiRD treatment has been completed.
Other Name: Revlimid
While new anti-myeloma therapies such as bortezomib and immunomodulatory drugs have been developed, multiple myeloma remains an incurable malignancy. Given that obtaining a complete remission (CR) with therapy will allow patients with newly diagnosed multiple myeloma to enjoy a higher quality of life and longer duration of freedom from disease symptoms, finding an optimally effective and well-tolerated regimen is imperative.
The robust overall response rate of 91% with the BiRD regimen for patients with newly diagnosed multiple myeloma is encouraging and we believe that by adding carfilzomib the overall response rate and CR rate can be improved. As carfilzomib has proven efficacy in myeloma and in patient's who have relapsed on bortezomib, we anticipate that it will synergize with the previous BiRD regimen to induce greater reduction of tumor burden overall.
The primary endpoints include best response rate, toxicities, progression free survival, event free survival, and overall survival. In those patients who are eligible for autologous stem cell transplantation, we will also study the effect of carfilzomib on CD 34+ stem cell yield following mobilization.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01559935
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10021|
|Principal Investigator:||Adriana Rossi, M.D.||Weill Medical College of Cornell University|