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

Pharmacyclics

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Dexamethasone; Drug: Ibrutinib; Drug: Pomalidomide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02548962

PCI-32765 (Other Identifier)

PCYC-1138-CA

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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11 participants in 3 patient groups

Phase 1: Dose Finding

Experimental group

Description:

Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO

Treatment:

Drug: Dexamethasone

Drug: Ibrutinib

Drug: Pomalidomide

Phase 2: Treatment Arm A

Experimental group

Description:

Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO

Treatment:

Drug: Dexamethasone

Drug: Ibrutinib

Drug: Pomalidomide

Phase 2: Treatment Arm B

Experimental group

Description:

Placebo PO+ Pomalidomide PO+ Dexamethasone PO

Treatment:

Drug: Dexamethasone

Drug: Pomalidomide

Drug: Placebo