Study of BTK Inhibitor, Ibrutinib in Combination With Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01962792
• Other study ID #: PCYC-1119-CA
• Secondary ID: Ibrutinib (PCI-3
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2013
• Est. completion date: March 2019

Study information

• Verified date: November 2021
• Source: Pharmacyclics LLC.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Ibrutinib

• Carfilzomib

• Dexamethasone

Locations

Country	Name	City	State
Canada	McGill University	Montreal	Quebec
United States	MUSC Hollings Cancer Center	Charleston	South Carolina
United States	Carolinas Healthcare System	Charlotte	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of California Los Angeles	Los Angeles	California
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Mount Sinai Hospital	New York	New York
United States	New York Presbyterian Hospital - Weill-Cornell	New York	New York
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Methodist Healthcare System	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacyclics LLC.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.	up to 4 years
Secondary	Duration of Response (DOR)	The time interval between the date of initial documentation of a response (PR or better) and the date of first documented evidence of progressive disease, death, or date of censoring for the subjects who had not progressed/died. The censoring date was the last adequate tumor assessment date.	Up to 4 years
Secondary	Overall Survival	Time from date of first dose of study treatment to the date of death from any cause	Up to 4 years
Secondary	Progression Free Survival (PFS)	Time from date of first dose of study treatment to the date of first documented evidence of progressive disease, death or date of censoring for the subjects not progressed/died. The censoring date was the last adequate tumor assessment date.	Up to 4 years