Clinical trial NCT01962792: Study of BTK Inhibitor, Ibrutinib in Combination With Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma
Official title: A Multicenter Phase 1/2b Study of the Bruton's Tyrosine Kinase Inhibitor, Ibrutinib (PCI-32765), in Combination With Carfilzomib (Kyprolis™) in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: PCI-32765
Multiple Myeloma
Relapsed Refractory Multiple Myeloma
Bruton's Tyrosine Kinase
Carfilzomib
Dexamethasone
Ibrutinib
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2013-10-14
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A MULTICENTER PHASE 1/2B STUDY OF THE BRUTON'S TYROSINE KINASE INHIBITOR, IBRUTINIB (PCI-32765), IN COMBINATION WITH CARFILZOMIB (KYPROLIS™) IN SUBJECTS WITH RELAPSED OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA

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 relapsed or relapsed and refractory multiple myeloma (MM).

Eligibility 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, 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:

  1. Achieved less than a partial response (\<PR) following at least 4 cycles and are without evidence of progression disease (PD).

     OR
  2. 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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: up to 4 years
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to 4 years
measure: Overall Survival
timeFrame: Up to 4 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: New York Presbyterian Hospital - Weill-Cornell
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare System
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
References: