Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Bruton's Tyrosine Kinase, PCI-32765, Pomalidomide, Dexamethasone, Relapsed Refractory Multiple Myeloma, Ibrutinib
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.
Interventions
DRUGIbrutinib
DRUGPomalidomide
DRUGDexamethasone
DRUGPlacebo
Sponsors
Celgene Corporation
Pharmacyclics LLC.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Czechia, Germany, Greece, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Dose Finding (560mg) Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Ibrutinib (560mg)
Pomalidomide (4mg)
Dexamethasone (40mg) | 8 |
| Phase 1: Dose Finding (840mg) Ibrutinib PO+ Pomalidomide PO+ Dexamethasone PO
Ibrutinib (840mg)
Pomalidomide (4mg)
Dexamethasone (40mg) | 3 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Phase 1: Dose Finding (560mg) | Phase 1: Dose Finding (840mg) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 0 Participants | 5 Participants |
| Age, Continuous | 63.5 years | 72.7 years | 67.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Australia | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Czechia | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Greece | 3 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 3 participants | 0 participants | 3 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 5 Participants | 0 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 8 | 1 / 3 |
| other Total, other adverse events | 8 / 8 | 3 / 3 |
| serious Total, serious adverse events | 8 / 8 | 3 / 3 |
Outcome results
Primary
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
Time frame: 14 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Dose Finding (560mg) | Overall Response Rate (ORR) According to the IMWG Response Criteria Per Investigator Assessment | 3 Participants |
| Phase 1: Dose Finding (840mg) | Overall Response Rate (ORR) According to the IMWG Response Criteria Per Investigator Assessment | 1 Participants |
Secondary
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.
Time frame: 14 Months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: Dose Finding (560mg) | Clinical Benefit Response (CBR) | 4 Participants |
| Phase 1: Dose Finding (840mg) | Clinical Benefit Response (CBR) | 2 Participants |
Secondary
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.
Time frame: 14 Months
Population: Median was not reached for Phase 1: Dose Finding (560 mg). Median value provided here was the median and range (min and max).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1: Dose Finding (560mg) | Duration of Response (DOR) | 6.5 Months |
| Phase 1: Dose Finding (840mg) | Duration of Response (DOR) | 7.3 Months |