E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Refractory or relapsed and refractory multiple myeloma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of pomalidomide (CC-4047) monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who discontinued from Treatment Arm B (dexamethasone alone) of Study CC-4047-MM-003 due to the development of documented disease progression during treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of pomalidomide monotherapy in subjects with refractory or relapsed and refractory multiple myeloma who discontinued treatment after being treated in the dexamethasone alone arm (Treatment Arm B) in Study CC-4047-MM-003 due to the development of documented disease progression during treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects with refractory or relapsed and refractory multiple myeloma who were enrolled in Study CC-4047-MM-003 and discontinued study therapy with dexamethasone alone (Treatment Arm B) after at least two cycles of dexamethasone treatment and due to development of documented disease progression according to the IMWG criteria and as decided by an IRAC. 2. Must be ? 18 years at the time of signing the informed consent form. 3. The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted. The only exception is if a skeletal survey was performed within 90 days prior to the start of Cycle 1, then a new survey will not be required. 4. Must be able to adhere to the study visit schedule and other protocol requirements. 5. Subjects must have documented diagnosis of multiple myeloma and have measurable disease (serum M-protein ? 1.0 g/dL or urine M-protein ? 200 mg/24 hours). However, for subjects with IgA multiple myeloma, a serum M-protein of ? 0.5 g/dL or urine M-protein ? 200 mg/24 hours will be eligible for the study. 6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 7. Females of childbearing potential (FCBP) 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 from the study drug and must agree to regular pregnancy testing during this timeframe. 8. Females must agree to abstain from breastfeeding during study participation and 28 days after study discontinuation. 9. 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. 10. Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study treatment. 11. All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment. 12. All subjects must agree not to share study medication. |
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E.4 | Principal exclusion criteria |
1. Subjects with multiple myeloma who were not treated as a part of Study CC-4047-MM-003 (Arm B). 2. Subjects who received any treatments (steroids, anti-myeloma, or anti-cancer therapy) within the last 14 days of wash-out period before initiation of study treatment. 3. Subjects who discontinued CC-4047-MM-003 study ?120 days. 4. Subjects who initiate another anti-myeloma therapy from the time of disease progression on study CC-4047-MM-003 to the time of treatment initiation in the companion study. 5. 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; or a platelet count < 30,000/µL for subjects in whom ? 50% of bone marrow nucleated cells are plasma cells ? Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula ? Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L); or free ionized calcium > 6.5 mg/dL (> 1.6 mmol/L) ? Hemoglobin ? 8 g/dL (? 4.96 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted) ? Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN) ? Serum total bilirubin > 2.0 mg/dL 6. Prior history of malignancies, other than MM, unless the subject 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) 7. Hypersensitivity to thalidomide or lenalidomide 8. Peripheral neuropathy ? Grade 2. 9. Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant. 10. Subjects who are planning for or who are eligible for stem cell transplant. 11. Subjects with any one of the following: ? Congestive heart failure (NY Heart Association Class III or IV) ? Myocardial infarction within 12 months prior to starting study treatment ? Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris 12. Subjects who received any of the following within the last 14 days of initiation of study treatment: ? Plasmapheresis ? Major surgery (kyphoplasty is not considered major surgery) ? Radiation therapy 13. Use of any investigational agents within 28 days or 5 half lives (whichever is longer) of treatment. 14. Subjects with chronic conditions such as rheumatoid arthritis, multiple sclerosis and lupus. 15. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 16. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide. 17. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment. 18. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. 19. Pregnant or breastfeeding females. 20. Known HIV positivity or active infectious hepatitis A, B or C. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is overall response rate (ORR) using the new International Myeloma Working Group Uniform (IMWG) response criteria. An analysis comparing the results of response assessments judged by the EMBT criteria (Blade, 1998) to those of the IMWG criteria will also be performed. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 64 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |