Myeloproliferative Neoplasm (MPN) Associated Myelofibrosis defined as primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF) and post-essential thrombocythemia myelofibrosis (post-ET MF) MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years of age at the time of signing the informed consent document. 2. MPN-associated myelofibrosis (primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF) and/or post-essential thrombocythemia myelofibrosis (post-ET MF) 3. RBC-transfusion-dependence: - Average RBC-transfusion frequency of =2 U/28 days over at least the 84 days immediately prior to randomization. There must be no interval >42 days without =1 RBC-transfusion. - Only RBC-transfusions given when the hemoglobin =90 g/L^3 are scored in determining eligibility. - RBC-transfusions due to bleeding are not scored in determining eligibility - RBC-transfusions due to chemotherapy-induced anemia are not scored in determining eligibility. 4. Hemoglobin =130 g/L at randomization. 5. Bone marrow slides that meet defined criteria for central histological review will be submitted to a central reviewer. 6. A blood cell or bone marrow allo-transplant should not be an appropriate therapy at this time. 7. Erythropoietin should not be an appropriate therapy at this time. 8. Androgenic steroids should not be an appropriate therapy at this time. 9. Treatment with systemic corticosteroids is permitted for non-hematological conditions providing the subject is receiving a stable or decreasing dose for =84 days immediately prior to randomization and are receiving a constant dose equivalent to =10 mg prednisone for the 28 days immediately prior to randomization. 10. Eastern Cooperative Oncology Group (ECOG) performance score =2. 11. Females of childbearing potential (FCBP) must undergo pregnancy testing based on the frequency outlined in protocol Appendix 18.1 and pregnancy results must be negative. 12. Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods as specified in protocol Appendix 18.1. 13. Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP as specified in Appendix 18.1. 14. Males must agree not to donate semen or sperm during the duration specified in Appendix 18.1. 15. All subjects must: - Understand that the investigational product could have a potential teratogenic risk. - Agree to abstain from donating blood while taking investigational product and following discontinuation of investigational product - Agree not to share study medication with another person. - Be counseled about pregnancy precautions and risks of fetal exposure. 16. Understand and voluntarily sign an informed consent document before any study related assessments/procedures are conducted. 17. Able to adhe
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a subject from enrollment: 1. Prior bone marrow or blood cell transplant. 2. Use of drugs to treat MPN-associated myelofibrosis =30 days pre-randomization(42 days for hydroxyurea) or ongoing adverse events from previous treatment. 3. Use of an erythropoietin or androgenic steroids =84 days pre- randomization. 4. Anemia from other proved causes other than MPN-associated myelofibrosis. 5. Pregnant or lactating females. 6. More than 10% blasts by bone marrow examination or more than 10% blasts in blood in consecutive measurements spanning at least 8 weeks. 7. Prior history of malignancies, other than the disease being studied, unless the subject has been free of the malignancy for = 5 years with the following exceptions: -Basal cell carcinoma of the skin, -Squamous cell carcinoma of the skin -Carcinoma in situ of the cervix -Carcinoma in situ of the breast -Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) 8. Proved human immunodeficiency virus-1 (HIV-1) infection 9. Active hepatitis B virus (HBV) or active hepatitis C Virus (HCV) infection. 10. Prior therapy with pomalidomide. 11. Any of the following adverse reactions to prior therapy with thalidomide or lenalidomide: - Prior =grade-2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) allergic reaction to thalidomide and/or lenalidomide - Prior desquamating (blistering) rash while taking thalidomide and/or lenalidomide - Hypersensitivity to thalidomide and lenalidomide 12. Any of the following laboratory abnormalities: -Neutrophils 3.0 x upper limit of normal (ULN) - Total bilirubin = 4 x ULN; - Uncontrolled hyperthyroidism or hypothyroidism. 13. Deep venous thrombosis (DVT) or pulmonary embolus (PE) II, congestive heart failure - Unstable angina - Myocardial infarction within 6 months 15. Any significant medical condition, laboratory abnormality or psychiatric illness that would prevent the subject from participating in the study. 16. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 17. Any condition that confounds the ability to interpret data from the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Compare efficacy of pomalidomide versus placebo in achieving Red Blood Cell (RBC)-transfusion-independence in subjects with Myeloproliferative neoplasm-associated myelofibrosis with RBC-transfusion-dependence.; Secondary Objective: Evaluate safety of pomalidomide in subjects with MPN-associated myelofibrosis with RBC-transfusion-dependence. ;Primary end point(s): Proportion of subjects achieving = 84 consecutive days of RBC-transfusion-independence; Timepoint(s) of evaluation of this end point: At the end of study week 24 (Day 169) then, every 28 days until relapse or discontinuation for any reason. Group analysis: when the last subject randomized reaches Day 169 evaluation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Duration of RBC-transfusion-independence 2) Time to becoming RBC-transfusion-independent 3) Survival - alive or dead 4) Frequency of AE's 5) Healthcare resource utilization 6) EQ-5D Health Outcome Assessment 7) FACT-An Quality of Life (QoL) Assessment ; Timepoint(s) of evaluation of this end point: 1) Every 28d until relapse/discontinuation for any reason; 2) Every 28d until all responders are identified; 3) Every 4months during the first 2 years following treatment discontinuation, then every 6 months until 5 years after subject was randomized; 4) & 5) every 28d until 28d after subject’s final dose of study medication; 6) At Day 1, 85, 169 and at treatment discontinuation; 7) At D1, D84 and every 84d while on treatment and at treatment discontinuation 1st analysis of all endpoints: when all subjects have completed the blinded treatment phase. 2nd analysis: 2 years after the last subject was randomized. 3rd analysis: 5 years after the last subject was randomized | — |
Countries
Australia, Austria, Belgium, Canada, China, Germany, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinicalTrialDisclosure
Celgene Corporation
Outcome results
None listed