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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ibrutinib
Carfilzomib
Dexamethasone
Sponsored by
Pharmacyclics LLC.
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase 1 - Dose Finding

Phase 2b - Main Study

Phase 2b - Sub-study

Arm Description

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

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)
-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.

Secondary Outcome Measures

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.
Overall Survival
Time from date of first dose of study treatment to the date of death from any cause
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.

Full Information

First Posted
September 27, 2013
Last Updated
November 24, 2021
Sponsor
Pharmacyclics LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT01962792
Brief Title
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

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
December 2013 (Actual)
Primary Completion Date
March 2019 (Actual)
Study Completion Date
March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
PCI-32765, Multiple Myeloma, Relapsed Refractory Multiple Myeloma, Bruton's Tyrosine Kinase, Carfilzomib, Dexamethasone, Ibrutinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
84 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1 - Dose Finding
Arm Type
Experimental
Arm Description
Ibrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg
Arm Title
Phase 2b - Main Study
Arm Type
Experimental
Arm Description
Ibrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg
Arm Title
Phase 2b - Sub-study
Arm Type
Experimental
Arm Description
Ibrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.
Time Frame
up to 4 years
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Description
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.
Time Frame
Up to 4 years
Title
Overall Survival
Description
Time from date of first dose of study treatment to the date of death from any cause
Time Frame
Up to 4 years
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
Up to 4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
New York Presbyterian Hospital - Weill-Cornell
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Mount Sinai Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Carolinas Healthcare System
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
MUSC Hollings Cancer Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Vanderbilt Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Methodist Healthcare System
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
QC H4A 3J1
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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