Study of Ibrutinib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma

Phase 1

Terminated

• Conditions: Multiple Myeloma
• Interventions: Drug: Ibrutinib; Drug: Pomalidomide; Drug: Placebo; Drug: Dexamethasone

• Registration Number: NCT02548962
• Lead Sponsor: Pharmacyclics LLC.

Brief Summary

Phase 1 is an open-label, dose finding, multicenter study of ibrutinib in combination with pomalidomide and dexamethasone in subjects with relapsed/refractory multiple myeloma.

Phase 2b is a randomized, double-blind, multicenter study of ibrutinib or placebo, in combination with pomalidomide and dexamethasone in subjects with relapsed/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. Ibrutinib 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 ibrutinib in combination with pomalidomide and dexamethasone in subjects with relapsed/refractory multiple myeloma.

Study Timeline

• Study First Submitted: 2015-09-03
• Study First Submitted QC: 2015-09-10
• Study First Posted: 2015-09-14
• Study Start: 2016-03
• Primary Completion: 2018-06-13
• Study Completion: 2018-06-13
• Results First Submitted: 2019-03-20
• Results First Submitted QC: 2019-04-18
• Results First Posted: 2019-04-23
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-04
• Last Update Posted: 2019-11-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

• Subjects with relapsed/refractory MM who have received at least two prior lines of therapy including lenalidomide and either bortezomib or carfilzomib and have demonstrated disease progression on or within 60 days of the completion of the most recent treatment regimen.

• Measurable disease defined by at least ONE of the following:

  1. Serum monoclonal protein (SPEP) ≥1 g/dL.
  2. Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine.

• Adequate hematologic, hepatic, 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 treatment with strong CYP3A inhibitors
• Women who are pregnant or breast feeding.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2: Treatment Arm B	Placebo	Placebo PO+ Pomalidomide PO+ Dexamethasone PO
Phase 1: Dose Finding	Dexamethasone	Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Phase 1: Dose Finding	Ibrutinib	Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Phase 1: Dose Finding	Pomalidomide	Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Phase 2: Treatment Arm A	Pomalidomide	Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Phase 2: Treatment Arm A	Ibrutinib	Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Phase 2: Treatment Arm A	Dexamethasone	Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Phase 2: Treatment Arm B	Pomalidomide	Placebo PO+ Pomalidomide PO+ Dexamethasone PO
Phase 2: Treatment Arm B	Dexamethasone	Placebo PO+ Pomalidomide PO+ Dexamethasone PO

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) According to the IMWG Response Criteria Per Investigator Assessment	14 Months	The overall response rate, defined as the proportion of subjects achieving a best overall response of PR or better per investigator assessment per IMWG at or prior to initiation of subsequent anticancer therapy

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Response (CBR)	14 Months	The clinical benefit response, defined as the proportion of subjects achieving a best overall response of MR or better per investigator assessment per IMWG at or prior to initiation of subsequent anticancer therapy.
Duration of Response (DOR)	14 Months	The time interval between the date of initial documentation of a response and the date of first documented evidence of progressive disease, death, or date of censoring for the subjects not progressed/died. The censoring date is the last adequate tumor assessment date.

Trial Locations

Locations (16)

City of Hope; 🇺🇸 Duarte, California, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Concord Repatriation General Hospital; 🇦🇺 Concord, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Fakultni nemocnice Brno; 🇨🇿 Brno, Czechia

Fakultni nemocnice Ostrava; 🇨🇿 Ostrava, Czechia

Vseobecna fakultni nemocnice v Praze; 🇨🇿 Praha, Czechia

Clinica Universidad de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Universitätsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Germany

Hospital de La Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

'Alexandra' General Hospital of Athens; 🇬🇷 Athens, Attiki, Greece

Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Hospital Universitario Doctor Peset; 🇪🇸 Valencia, Spain

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States