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, 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 on Days 1, 8, 15 and 22 of each 28-day cycle for subjects who were ≤ 75 years of age. For subjects who were > 75 years of age, the starting dose of dexamethasone was 20 mg once per day on Days 1, 8, 15 and 22 of each 28-day cycle. As prophylactic anti-thrombotic treatment, all participants were to be given aspirin 81-100 mg daily (commercial supply) unless contraindicated. If aspirin was contraindicated, participants were to receive another form of anti-thrombotic therapy according to hospital guidelines or physician preference.
Participants in the 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 confirmed PD 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, at which point they were discontinued.
Upon discontinuation from study treatment for PD or any other reason, participants were to be assessed three times per year (April, August and December), up to five years, for survival 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. Data cut-off for the interim analysis was 29 October 2010. For the interim analysis, results using aggregated data were provided by Celgene, and analyses by treatment arm were performed by an independent statistician for the Data Monitoring Committee (DMC). The DMC recommended that Celgene personnel be unblinded based on the strength of the data. Limited Celgene personnel were unblinded and shared that unblinded data during a meeting with the FDA. Subsequently, Celgene decided to file an application based on more current study data; the data cut-off for the application was 1 April 2011. The product was approved by the FDA in February 2013 based on data from the 01 April 2011 data cut-off. Results from the 01 April 2011 data cut-off are reported.
The study continues. A final analysis will be performed when the study is completed and results reported as available.
Inclusion Criteria:
- Must be greater than or equal to 18 years at the time of signing the informed consent form
- Must be able to adhere to the study visit schedule and other protocol requirements
- Have a documented diagnosis of multiple myeloma and have relapsed and refractory disease. Patients must have received at least 2 prior therapies. Patients must have relapsed after having achieved at least stable disease for at least one cycle of treatment to at least one prior regimen and then developed PD. Patients must also have documented evidence of PD during or within 60 days (measured from the end of the last cycle) of completing treatment with the last anti-myeloma drug regimen used just prior to study entry (refractory disease)
- Patients must have also undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or within the same regimen)
- Measurable levels of myeloma paraprotein in serum (greater than or equal to 0.5 g/dL) or urine (greater than or equal 0.2 g/dL excreted in a 24 hour collection sample)
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Females of childbearing potential (FCBP) [An FCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months)] must agree to refrain from becoming pregnant for 28 days prior to initiation of study drug, while on study drug and for 28 days after discontinuation of study drug and must agree to regular pregnancy testing during this timeframe.
- All patients must also agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study
- Males must agree to use a latex condom during any sexual contact with FCBP while participating in the study and for 28 days following discontinuation from this study even if he has undergone a successful vasectomy. Males must also agree to refrain from donating blood, semen or sperm during the above referenced timeframe.
- All patients must agree not to share medication with another person.
Exclusion Criteria:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form.
- Any serious concurrent medical conditions that may make the patient non-evaluable or put the patient's safety at risk.
- Pregnant or lactating females
- Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) < 1,000 cells/mm3
- Platelet count < 75,000/mm3 for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/mm3 for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells
- Serum creatinine > 3.0 mg/dL
- Serum glutamic oxaloacetic transaminase/Aspartate transaminase (SGOT/AST) or Serum Glutamic Pyruvate Transaminase/Alanine transaminase (SGPT/ALT) > 3.0 X upper limit of normal (ULN)
- Serum total bilirubin > 2.0 mg/dL
- Prior history of malignancies, other than multiple myeloma, unless the patient has been free of the disease for ≥ 3 years. Exceptions include the following:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix or breast
- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
- Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C Virus (HCV) infection
- Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
- Peripheral neuropathy ≥ Grade 2
- Use of any anti-myeloma drug therapy within 14 days of the initiation of study drug treatment or use of any experimental non-drug therapy within 28 days of the initiation of study drug treatment
- Radiation therapy within 14 days of initiation of study drug treatment Inability or unwillingness to comply with birth control requirements
Last updated: 05/01/2013
NCT ID: NCT00833833
IRB Number:08-005968
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