Clinical trial NCT02548962: Study of Ibrutinib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma
Official title: A Randomized Multicenter Study of Ibrutinib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Bruton's Tyrosine Kinase
PCI-32765
Pomalidomide
Dexamethasone
Relapsed Refractory Multiple Myeloma
Ibrutinib
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
Collaborators: name: Celgene Corporation
First posted: 2015-09-14
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR) According to the IMWG Response Criteria Per Investigator Assessment
timeFrame: 14 Months
Secondary outcomes:
measure: Clinical Benefit Response (CBR)
timeFrame: 14 Months
measure: Duration of Response (DOR)
timeFrame: 14 Months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Ostrava
country: Czechia
facility: Fakultni nemocnice Ostrava
city: Praha
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
city: Athens
country: Greece
facility: 'Alexandra' General Hospital of Athens
state: Attiki
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
Study officials:
References: