Clinical trial NCT00833833
Conditions: Multiple Myeloma
Sponsor: Celgene Corporation
Start date: 2008-06-01; Completion date: 2015-09-01
Enrollment: 259 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine the maximum tolerated dose and effectiveness of the study drug (CC-4047) Alone Or in Combination With Low-dose Dexamethasone as treatment for patients with relapsed and refractory multiple myeloma

Detailed description:
The Phase 1 segment of the study was designed to determine the maximum tolerated dose (MTD) of single-agent pomalidomide, which was to be determined in the first cycle of treatment. Following completion of the first cycle, participants were allowed to continue the study at their assigned dose of pomalidomide.

Participants who developed progressive disease (PD) at any time, or who had not achieved at least a 25% reduction of serum myeloma (M)-protein levels (if measurable) and a 50% reduction of urine M-protein (if measurable) compared with baseline after completion of 4 cycles of pomalidomide, had the option to receive oral dexamethasone 40 mg on days 1, 8, 15, and 22 of each 28-day treatment cycle in addition to their current dose of pomalidomide. Participants with PD who chose not to add dexamethasone to pomalidomide therapy were to be discontinued from the study. Participants who chose to add dexamethasone were allowed to continue study treatment until PD developed again, unacceptable toxicity or participant withdrew consent, at which time they were to be discontinued.

Based on results from the phase 1 portion, the Data Monitoring Committee confirmed 4 mg/day as MTD of pomalidomide. Therefore, the recommended starting dose of pomalidomide for Phase 2 was 4 mg/day on Days 1-21 of each 28-day cycle. In the combination treatment arm, the starting dose of dexamethasone was 40 mg once per day. For subjects who were \> 75 years of age, the starting dose of dexamethasone was 20 mg once per day. To prevent blood clots, all participants were to be given aspirin 81-100 mg daily (commercial supply) unless contraindicated. If contraindicated, another form of anti-thrombotic therapy was provided.

Participants in the Phase II combination treatment arm could continue study treatment until PD developed, at which time they were to be discontinued. Participants in the single agent pomalidomide treatment arm who developed PD, confirmed by the IRAC, at any time had the option to receive oral dexamethasone in addition to their current dose of pomalidomide at the starting dose described above. Participants with PD who chose not to add dexamethasone to pomalidomide therapy were discontinued from study treatment. Participants who chose to add dexamethasone to pomalidomide therapy could continue study treatment until PD developed again, unacceptable toxicity or participant withdrew consent, at which point they were discontinued.

Upon discontinuation from study treatment for PD or any other reason, participants were to be assessed two times per year, up to five years, for survival, second primary malignancy and subsequent anti-myeloma therapies.

Two analyses were planned during the course of the Phase 2 segment: one interim analysis (at 50% information of progression-free survival (PFS) events) and one final analysis. The Data Monitoring Commmittee recommended that Celgene personnel be unblinded based on the strength of the data. Subsequently, Celgene decided to file an application based on more current study data. The product was approved by the FDA in February 2013.

Since no further analyses are required per protocol nor to support the marketing application, the study was amended to remove undue burden from patients who remain on active treatment by ending the treatment segments of this study and transferring all active patients tothe Long-term Follow-up Phase. These patients who continue to be treated with pomalidomide will be provided Pomalyst through the Celgene Patient Support Program (Pomalyst REMSTM) until disease progression, unacceptable toxicity, the investigator decides to change therapy or patient decision. Investigators will treat their patients according to the local standard of care and follow the assessments required for patients in the Long-term Follow-up Phase. These assessments include subsequent myeloma therapies, second primary malignancies and survival.

The study continues. A final analysis will be performed when the study is completed and results reported as available.

Arms: arm 1: Pomalidomide 2 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. arm 2: Pomalidomide 3 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. arm 3: Pomalidomide 4 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. arm 4: Pomalidomide 5 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. arm 5: Combination therapy of 4 mg pomalidomide given once per day on Days 1-21 of each 28-day cycle and the starting dose of dexamethasone (determined by age) on days 1, 8, 15, and 22 of each 28-day cycle. The starting dose of dexamethasone was 40 mg for participants who were ≤ 75 years of age and 20 mg for participants who were \> 75 years of age. Dose reduction steps for dexamethasone were provided for drug-related toxicities. arm 6: 4 mg pomalidomide was given once per day on Days 1-21 of each 28-day cycle until PD. Participants in the single agent pomalidomide treatment arm who developed confirmed PD at any time had the option to receive oral dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle at the starting dose of 20 or 40 mg depending on age in addition to their current dose of pomalidomide, or to discontinue treatment.
Interventions: intervention 1: Pomalidomide intervention 2: Dexamethasone intervention 3: Aspirin
Intervention descriptions: intervention 1: 1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply intervention 2: oral dexamethasone intervention 3: As prophylactic anti-thrombotic treatment, all participants were given aspirin 81-100 mg daily (commercial supply) unless contraindicated. If aspirin was contraindicated, participants were given another form of anti-thrombotic therapy according to hospital guidelines or physician preference.

Protocol documents: