Study of BTK Inhibitor, Ibrutinib in Combination With Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma
Multiple Myeloma
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring PCI-32765, Multiple Myeloma, Relapsed Refractory Multiple Myeloma, Bruton's Tyrosine Kinase, Carfilzomib, Dexamethasone, Ibrutinib
Eligibility Criteria
Inclusion Criteria:
Measurable disease of MM as defined by at least ONE of the following:
- Serum monoclonal protein (SPEP) ≥1 g/dL
- Urine M-protein ≥200 mg/24 hrs
- Serum free light chain (SFLC): involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal kappa to lambda serum free light chain ratio
- Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies, including an immunomodulator and bortezomib and had either no response or documented disease progression (according to IMWG criteria) to the most recent treatment regimen
- Adequate hematologic, hepatic, and renal function
- ECOG performance status of 0-2
Inclusion Criteria for Phase 2 Sub-study Cohort:
- Must meet all inclusion criteria defined in main study and in addition the following criteria must be met:
Subject must have received a regimen containing carfilzomib in combination with dexamethasone as their most recent line of therapy and have:
Achieved less than a partial response (<PR) following at least 4 cycles and are without evidence of progression disease (PD).
OR
- Disease progression following an initial confirmed response of MR or better to the combination (according to IMWG response criteria).
Exclusion Criteria:
- Subject must not have primary refractory disease
- Plasma cell leukemia, primary amyloidosis or POEMS syndrome
- Unable to swallow capsules or disease significantly affecting gastrointestinal function
- Requires anti-coagulation with warfarin or a vitamin K antagonist
- Requires treatment with strong CYP3A inhibitors
Exclusion Criteria for Phase 2 Sub-study Cohort:
- Must not meet any exclusion criteria defined in main study except for exclusion criteria "Subject must not have primary refractory disease" which is related to prior carfilzomib
Sites / Locations
- City of Hope
- University of California Los Angeles
- Colorado Blood Cancer Institute
- University of Nebraska Medical Center
- New York Presbyterian Hospital - Weill-Cornell
- Mount Sinai Hospital
- Carolinas Healthcare System
- Duke University Medical Center
- University of Cincinnati
- Cleveland Clinic
- Thomas Jefferson University
- MUSC Hollings Cancer Center
- Vanderbilt Ingram Cancer Center
- University of Texas Southwestern Medical Center
- Methodist Healthcare System
- Virginia Commonwealth University
- McGill University
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Phase 1 - Dose Finding
Phase 2b - Main Study
Phase 2b - Sub-study
Ibrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg
Ibrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg
Ibrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg