E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsed or refractory multiple myeloma (MM) |
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E.1.1.1 | Medical condition in easily understood language |
(Blood cancer) certain blood cells multiply abnormally in the bone marrow, impair the production of other blood cells and produce proteins that cumulate in other organs impairing their functioning |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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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 compare the efficacy of POM + BTZ + LD-DEX with BTZ + LD-DEX in subjects with relapsed or refractory MM |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and additional efficacy of POM + BTZ + LD-DEX versus BTZ + LD-DEX in subjects with relapsed or refractory MM. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Must be ≥ 18 years at the time of signing the informed consent form. 2. The subject must understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures. 3. Must be able to adhere to the study visit schedule and other protocol requirements. 4. Subjects must have documented diagnosis of multiple myeloma and have measurable disease by serum or urine protein electrophoresis (sPEP or uPEP): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours. 5. All subjects must have had at least 1 but no greater than 3 prior anti-myeloma regimens. (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one regimen.) 6. All subjects must have documented disease progression during or after their last anti-myeloma therapy. 7. All subjects must have received prior treatment with a lenalidomide-containing regimen for at least 2 consecutive cycles. 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. 9. Females of childbearing potential (FCBP†) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact for at least 4 weeks before starting study treatment, while participating in the study (including dose interruptions), and for at least 4 weeks after study treatment discontinuation, and must agree to regular pregnancy testing during this timeframe. 10. Females must agree to abstain from breastfeeding during study participation and 4 weeks after study treatment discontinuation. 11. Males must agree to use a latex or synthetic condom during any sexual contact with FCBP while participating in the study and for 4 weeks following discontinuation from this study, even if he has undergone a successful vasectomy. 12. Males must also agree to refrain from donating sperm while on pomalidomide and for 4 weeks after discontinuation from this study treatment. 13. All subjects must agree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment. 14. All subjects must agree not to share medication.
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E.4 | Principal exclusion criteria |
1. Subjects who had documented progressive disease during therapy or within 60 days of the last dose of a bortezomib-containing therapy under the 1.3 mg/m2 dose twice weekly dosing schedule 2. Peripheral neuropathy Grade 3, Grade 4 or Grade 2 with pain within 14 days prior to randomization 3. Non-secretory multiple myeloma 4. Any of the following laboratory abnormalities: • Absolute neutrophil count (ANC) < 1,000/µL • Hemoglobin < 8 g/dL (< 4.9 mmol/L) • 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 • Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L) • Serum SGOT/AST or SGPT/ALT > 3.0 x upper limit of normal (ULN) • Serum total bilirubin > 1.5 x ULN 5. Subjects with severe renal impairment (Creatinine Clearance [CrCl] <30 mL/min) requiring dialysis 6. Subjects with prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the following non-invasive malignancies: • 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) or prostate cancer that is curative. 7. Previous therapy with pomalidomide 8. History of anaphylaxis or hypersensitivity to thalidomide, lenalidomide, bortezomib, boron, mannitol, or dexamethasone 9. ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy 10. Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide 11. Subjects with any one of the following: • Clinically significant abnormal ECG finding at screening • Congestive heart failure (New York 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 other than local therapy for myeloma associated bone lesions • Use of any systemic anti-myeloma drug therapy 13. Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment 14. Subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis, and lupus, which likely need additional steroid or immunosuppressive treatments in addition to the study treatment. Includes subjects receiving corticosteroids (> 10 mg/day of prednisone or equivalent) within 3 weeks prior to enrollment. 15. Subjects unable or unwilling to undergo protocol required thromboembolism prophylaxis or herpes zoster prophylaxis will not be eligible to participate in this 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 serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form 18. Pregnant or breastfeeding females 19. Known seropositive for or active viral infection with human immunodeficiency virus (HIV) 20. Known active viral infection with hepatitis A virus (HAV). 21. Known seropositive for or active viral infection with hepatitis B virus (HBV): • Subjects who are HBsAg negative and viral DNA negative are eligible. • Subjects who had hepatitis B but have received an antiviral treatment and show non-detectable viral DNA for 6 months are eligible. • Subjects who are seropositive because of hepatitis B virus vaccine are eligible. 22. Known seropositive for or active viral infection with hepatitis C virus (HCV): • Subjects who had hepatitis C but have received an antiviral treatment and show no detectable viral RNA for 6 months are eligible.
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-Free Survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PFS will be assessed by: - Bone Marrow Aspiration and/or Biospy – Screening and as Clinically indicated or to confirm CR - Quantitative Serum Immunoglobulins, serum-protein electrophoresis (sPEP), 24-hour urine protein electrophoresis, serum and urine immunofixation, serum free light-chain assay, and extramedullary plasmacytoma (EMPs) at Screening and Day 1 of each cycle and PFS Follow-up (if applicable). If EMPs are only assessable radiographically, scans are to be conducted at Screening, C3D1, every 3 cycles thereafter during treatment, at treatment discontinuation, every 63 days (3 cycles) during the PFS follow-up phase, at PFS follow-up phase discontinuation, and when clinically indicated to confirm response (> or = PR) -Skeletal Surveys – Screening and when clinically indicated
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E.5.2 | Secondary end point(s) |
-Overall Survival (OS) -Safety (type, frequency, seriousness and severity of AEs, and relationship of AEs to study drug or comparator) -Overall response rate (ORR) (using the International Myeloma Working Group Uniform [IMWG] response criteria) -Duration of response
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OS: All long-term follow-up phase subjects will be contacted four (4) times a year (every 3 months) to obtain survival status for at least 5 years after the last subject is randomized into the study, or longer if clinically indicated Safety: i. AEs: After signing ICF and until 28 days after treatment discontinuation; ii. SPM: After signing ICF up to and including the long-term follow-up period and up to 5 years after last subject enrolled Overall Response Rate (ORR): when assessable Duration of Response: when assessable |
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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 | Yes |
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 | Yes |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 100 |
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 | No |
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 |
Argentina |
Australia |
Austria |
Belgium |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
Japan |
Korea, Republic of |
Mexico |
Netherlands |
Norway |
Poland |
Portugal |
Puerto Rico |
Slovakia |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
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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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The End of Trial is defined as either the date of the last visit of the last subject to complete the study, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, whichever is the later date as pre-specified in the protocol and/or the Statistical Analysis Plan |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
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 |