Study of the Bruton's Tyrosine Kinase Inhibitor in Combination With Carfilzomib (Kyprolis™), in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
Conditions
Multiple Myeloma
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Conditions: Keywords
PCI-32765, Multiple Myeloma, Relapsed Refractory Multiple Myeloma, Bruton's Tyrosine Kinase, Carfilzomib, Dexamethasone
Study Type
Interventional
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Ibrutinib Type: Drug
Name: Carfilzomib Type: Drug
Name: Placebo Type: Drug
Name: Dexamethasone Type: Drug
Overall Status
Recruiting
Summary
Phase 1 is a dose escalation study to evaluate the safety and recommended Phase 2b dose of ibrutinib in combination with carfilzomib with and without dexamethasone.

Phase 2b will be a randomized, double-blind, placebo controlled study to evaluate the efficacy of ibrutinib and carfilzomib with or without dexamethasone.
Detailed Description
Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine, and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. PCI-32765 is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of PCI-32765 in combination with carfilzomib (Kyprolis™) with and without dexamethasone in subjects with MM.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Measurable disease of MM as defined by at least ONE of the following:

1. Serum monoclonal protein (SPEP) ≥1 g/dL

2. Urine M-protein >200 mg/24 hrs

3. 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 and renal function

- ECOG performance status of ≤ 2

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
Locations
City of Hope Medical Center
Duarte, California, United States
Status: Recruiting
University of California, Los Angeles
Los Angeles, California, United States
Status: Recruiting
Colorado Blood Cancer Institute
Denver, Colorado, United States
Status: Recruiting
Mount Sinai Medical Center
New York, New York, United States
Status: Recruiting
Weill Cornell Medical College
New York, New York, United States
Status: Recruiting
Carolinas Healthcare System
Charlotte, North Carolina, United States
Status: Active, not recruiting
Duke University
Durham, North Carolina, United States
Status: Recruiting
University of Cincinnati
Cincinnati, Ohio, United States
Status: Recruiting
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Status: Recruiting
Medical University of South Carolina
Charleston, South Carolina, United States
Status: Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Status: Recruiting
University of Texas Southwestern
Dallas, Texas, United States
Status: Recruiting
Virginia Commenwealth University
Richmond, Virginia, United States
Status: Recruiting
Start Date
December 2013
Sponsors
Pharmacyclics
Source
Pharmacyclics
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page