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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Randomized Multicenter Study of Ibrutinib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Ibrutinib
* Drug: Pomalidomide
* Drug: Dexamethasone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Serum monoclonal protein (SPEP) ≥1 g/dL. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose Finding<br>Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO | Drug: Ibrutinib<br> <br> Drug: Pomalidomide<br> <br> Drug: Dexamethasone<br> <br> |
| Experimental: Phase 2: Treatment Arm A<br>Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO | Drug: Ibrutinib<br> <br> Drug: Pomalidomide<br> <br> Drug: Dexamethasone<br> <br> |
| Experimental: Phase 2: Treatment Arm B<br>Placebo PO+ Pomalidomide PO+ Dexamethasone PO | Drug: Pomalidomide<br> <br> Drug: Dexamethasone<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) According to the IMWG Response Criteria Per Investigator Assessment | 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 | 14 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Response (CBR) | 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. | 14 Months | 
| Duration of Response (DOR) | 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. | 14 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Bruton's Tyrosine Kinase, PCI-32765, Pomalidomide, Dexamethasone, Relapsed Refractory Multiple Myeloma, Ibrutinib