Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments pomalidomide, dexamethasone
Phase phase 3
Sponsor Celgene Corporation
Start date March 2011
End date March 2013
Trial size 455 participants
Trial identifier NCT01311687, 2010-019820-30, CC-4047-MM-003

Summary

The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
For Subjects ≤ 75 years of age: 4 mg pomalidomide will be administered by mouth on Days 1-21 of each 28-day treatment cycle until disease progression and 40 mg low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression For Subjects > 75 years of age: 4 mg pomalidomide will be administered by mouth on Days 1-21 of each 28-day treatment cycle until disease progression and 20 mg low dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression
pomalidomide CC-4047
4 mg pomalidomide will be administered by mouth on Days 1-21 of each 28-day treatment cycle until disease progression
dexamethasone
For Subjects ≤ 75 years of age: 40 mg of low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression For Subjects > 75 years of age: 20 mg low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression
(Active Comparator)
For Subjects ≤ 75 years of age: 40 mg high-dose dexamethasone will be administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression For Subjects > 75 years of age: 20 mg high-dose dexamethasone will be administered by mouth once per day on Days 1 through 4, 9 through 7, and 17 through 20 of a 28-day cycle until disease progression
dexamethasone
For Subjects ≤ 75 years of age: 40 mg of low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression For Subjects > 75 years of age: 20 mg low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression

Primary Outcomes

Measure
Progression-free Survival (PFS)
time frame: From randomization until the data cut-off date of 07 September 2012. Maximum duration of follow-up for PFS assessments was 57 weeks.
Progression-free Survival (PFS) With a Later Cut-off Date
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum duration of follow-up for PFS assessments was 74 weeks.

Secondary Outcomes

Measure
Number of Participants With Adverse Events (AEs)
time frame: From first dose of study drug through to 30 days after the last dose, until the data cut-off date of 01 March 2013. Maximum time on treatment was 93 weeks.
Overall Survival
time frame: From randomization until the data cut-off date of 07 September 2012. Maximum time on follow-up for survival was 70 weeks.
Overall Survival With a Later Cut-off Date
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up for survival was 93 weeks.
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Percentage of Participants With Objective Response According to European Group for Blood and Marrow Transplantation (EBMT) Criteria
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Time to Progression
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Time to Response
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Duration of Response
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Time to the First Hemoglobin Improvement
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Time to Improvement in Bone Pain
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Time to Improvement in Renal Function
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Time to Improvement in Eastern Cooperative Oncology Group (ECOG) Performance Status
time frame: From randomization until the data cut-off date of 01 March 2013. Maximum time on follow-up was 93 weeks.
Change From Baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Domain
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Change From Baseline in the EORTC QLQ-C30 Physical Functioning Domain
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Change From Baseline in the EORTC QLQ-C30 Emotional Functioning Domain
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Change From Baseline in the EORTC QLQ-C30 Fatigue Domain
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Change From Baseline in the EORTC QLQ-C30 Pain Domain
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Change From Baseline in the European Organization for Research and Treatment of Cancer QoL Questionnaire for Patients With Multiple Myeloma (EORTC QLQ-MY20) Disease Symptoms
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Change From Baseline in the EORTC QLQ-MY20 Side Effects Domain
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Change From Baseline in the European Quality of Life-5 Dimensions (EQ-5D) Utility Index Score
time frame: Day 1 of Cycle 1 (Baseline), and Day 1 of Cycles 2, 3, 4, 5 and 6
Time to First Worsening of Quality of Life (QOL) Domains
time frame: Assessed on Day 1 of the first 6 treatment cycles.

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Must be ≥ 18 years of age - Subjects must have documented diagnosis of multiple myeloma and have measurable disease - Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy - Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy - All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib - All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response [≥ partial response (PR)] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen - Patients must have received adequate prior alkylator therapy - Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 - Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation - Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation - Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study - Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study Exclusion Criteria: - Any of the following laboratory abnormalities: - Absolute neutrophil count (ANC) < 1,000/μL - Platelet count < 75,000/ μL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells - Creatinine Clearance < 45 mL/min - Corrected serum calcium > 14 mg/dL - Hemoglobin ≤ 8 g/dL - Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or Transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN) - Serum total bilirubin > 2.0 mg/dL - Previous therapy with Pomalidomide - Hypersensitivity to thalidomide, lenalidomide, or dexamethasone - Resistance to high-dose dexamethasone used in the last line of therapy - Peripheral neuropathy ≥ Grade 2 - Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant - Subjects who are planning for or who are eligible for stem cell transplant - Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris - Subjects who received any of the following within the last 14 days of initiation of study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy - Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment - Subjects with conditions requiring chronic steroid or immunosuppressive treatment - Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study - Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide - Subjects unable or unwilling to undergo antithrombotic prophylactic treatment - Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form - Pregnant or breastfeeding females - Known Human Immunodeficiency Virus (HIV) positivity or active infectious hepatitis A, B or C

Additional Information

Official title A PHASE 3, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY TO COMPARE THE EFFICACY AND SAFETY OF POMALIDOMIDE IN COMBINATION WITH LOW-DOSE DEXAMETHASONE VERSUS HIGHDOSE DEXAMETHASONE IN SUBJECTS WITH REFRACTORY OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Celgene Corporation.
Location data was received from the National Cancer Institute and was last updated in July 2016.