Phase 2 Trial of Intensive Chemo-immunotherapy With Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab for Relapsed/Refractory Myeloma in the Context of Salvage Autologous Hematopoietic Cell Transplantation
Overview
- Phase
- Phase 2
- Intervention
- Carfilzomib
- Conditions
- Multiple Myeloma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 41
- Locations
- 12
- Primary Endpoint
- number of patients with complete remission (CR) rate
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
The purpose of this study is to test any good and bad effects of giving a combination of study drugs before and after autologous stem cell transplant.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must be capable, willing, and able to provide written, informed consent.
- •Age ≥ 18-years-old and \<= 75-years-old.
- •Histologic confirmation of multiple myeloma by the enrolling institution
- •Symptomatic myeloma that has progressed/relapsed after 1 to 3 prior lines of therapy
- •Patients who have received \<=1 cycle of therapy after most recent progression/relapse are eligible to enroll on study
- •Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted
- •Bisphosphonates are permitted
- •Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted
- •Prior treatment with radiotherapy is permitted
- •Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 4 weeks from last dose (on a trial or outside a trial) are eligible
Exclusion Criteria
- •Plasma cell leukemia (\>20% circulating plasma cells) during screening studies
- •POEMS syndrome
- •Pregnant or lactating females. Because there is a potential risk for adverse events nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide. These potential risks may also apply to other agents used in this study.
- •Uncontrolled hypertension or diabetes
- •Active hepatitis B or C infection
- •Patients with HBV core antibody positive, but HBV PCR negative are eligible if they are on medication for suppression of HBV reactivation
- •Patients with HCV antibody positive, but PCR negative are eligible.
- •Serologically positive HIV (testing required during screening)
- •Significant cardiovascular disease with NYHA Class III or IV symptoms, EF\<40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination. Echocardiogram will be performed during screening evaluation.
- •Moderate or severe pulmonary hypertension defined as PASP \>50 mm Hg
Arms & Interventions
Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
After receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.
Intervention: Carfilzomib
Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
After receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.
Intervention: Lenalidomide
Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
After receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.
Intervention: Dexamethasone
Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
After receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.
Intervention: Daratumumab
Carfilzomib, Lenalidomide, Dexamethasone and Daratumumab & HCT
After receiving four 28-day cycles of Dara-CRd, eligible patients will then undergo HCT with high dose melphalan conditioning. Sixty to ninety days after HCT, patients will receive another 4 cycles of Dara-CRd.
Intervention: autologous hematopoietic cell transplantation
Outcomes
Primary Outcomes
number of patients with complete remission (CR) rate
Time Frame: 3 years
Traditional Response Criteria from International Myeloma Working Group Criteria for Multiple Myeloma