MTD, Safety, and Efficacy of Pomalidomide (CC-4047) Alone or With Low-dose Dexamethasone in Patients With Relapsed and Refractory Multiple Myeloma
NCT ID: NCT00833833
Last Updated: 2016-04-27
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
259 participants
INTERVENTIONAL
2008-06-30
2015-09-30
Brief Summary
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A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Phase 1: 2 mg pomalidomide
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.
Pomalidomide
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Dexamethasone
oral dexamethasone
Aspirin
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.
Phase 1: 3 mg pomalidomide
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.
Pomalidomide
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Dexamethasone
oral dexamethasone
Aspirin
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.
Phase 1: 4 mg pomalidomide
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.
Pomalidomide
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Dexamethasone
oral dexamethasone
Aspirin
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.
Phase 1: 5 mg pomalidomide
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.
Pomalidomide
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Dexamethasone
oral dexamethasone
Aspirin
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.
Phase 2: pomalidomide + dexamethasone
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.
Pomalidomide
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Dexamethasone
oral dexamethasone
Aspirin
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.
Phase 2: pomalidomide
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.
Pomalidomide
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Dexamethasone
oral dexamethasone
Aspirin
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.
Interventions
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Pomalidomide
1 mg, 2 mg, and 5 mg capsules for oral administration packaged in bottles containing a 21-day supply
Dexamethasone
oral dexamethasone
Aspirin
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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 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
18 Years
ALL
No
Sponsors
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Celgene Corporation
INDUSTRY
Responsible Party
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Principal Investigators
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Lars A Sternas, MD
Role: STUDY_DIRECTOR
Celgene Corporation
Locations
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Mayo Clinic Arizona
Scottsdale, Arizona, United States
Colorado Blood Cancer Institute
Denver, Colorado, United States
Moffitt Cancer Center
Tampa, Florida, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Mass General Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer CenterDivision of Hematology/Oncology
Ann Arbor, Michigan, United States
Mayo Clinic - Arizona
Rochester, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Roswell Park Cancer Institute Department of Medicine
Buffalo, New York, United States
Mt. Sinai Hospital
New York, New York, United States
Ohio State University Arthur G. James Cancer Hospital
Columbus, Ohio, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Tom Baker Cancer Center
Calgary, Alberta, Canada
Cross Cancer Institute
Edmonton, Alberta, Canada
Vancouver General Hospital
Vancouver, British Columbia, Canada
Princess Margaret Hospital and University of Toronto
Toronto, Ontario, Canada
Royal Victoria Hosptial
Montreal, Quebec, Canada
Countries
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References
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Siegel DS, Weisel KC, Dimopoulos MA, Baz R, Richardson P, Delforge M, Song KW, San Miguel JF, Moreau P, Goldschmidt H, Cavo M, Jagannath S, Yu X, Hong K, Sternas L, Zaki M, Palumbo A. Pomalidomide plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal impairment: a pooled analysis of three clinical trials. Leuk Lymphoma. 2016 Dec;57(12):2833-2838. doi: 10.1080/10428194.2016.1177181. Epub 2016 Jun 7.
Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson KC. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32. doi: 10.1182/blood-2013-11-538835. Epub 2014 Jan 13.
Richardson PG, Siegel D, Baz R, Kelley SL, Munshi NC, Laubach J, Sullivan D, Alsina M, Schlossman R, Ghobrial IM, Doss D, Loughney N, McBride L, Bilotti E, Anand P, Nardelli L, Wear S, Larkins G, Chen M, Zaki MH, Jacques C, Anderson KC. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood. 2013 Mar 14;121(11):1961-7. doi: 10.1182/blood-2012-08-450742. Epub 2012 Dec 14.
Other Identifiers
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CC-4047-MM-002
Identifier Type: -
Identifier Source: org_study_id
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