E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary 1. Objective: To determine the duration of PFS in patients with multiple myeloma, after at least 1 prior treatment regimen, treated with bortezomib and vorinostat compared to patients treated with bortezomib and placebo. Hypothesis: Administration of vorinostat in combination with bortezomib will improve PFS compared with that achieved in patients treated with bortezomib and placebo. |
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E.2.2 | Secondary objectives of the trial |
Objective: To assess the tolerability of vorinostat administered in combination with bortezomib. Hypothesis: Administration of vorinostat in combination with bortezomib to patients with multiple myeloma will be generally well-tolerated as evidenced by accumulated safety data for this trial. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A patient must satisfy each of the following criteria in order to qualify for participation in the study: 1. Patient, or the patients legal representative, has voluntarily agreed to participate by giving written informed consent. For those institutions that do not allow a legal representative to provide consent on behalf of a patient, patients must be able to provide written informed consent for themselves. 2. Patient is ≥18 years of age on the day of signing informed consent. 3. Patient has an established diagnosis of multiple myeloma based on the myeloma diagnostic criteria located in Appendix 6.2. [9; 10] 4. Patient has received at least 1 but not more than 3 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen as per the European Blood and Marrow Transplantation Group (EBMT) Criteria located in Appendix 6.6 [11]. 5. Patient who received prior bortezomib-containing regimen and meets the following criteria is also eligible: While on prior bortezomib-based therapy, the patient must have achieved a minimal response (MR), partial response (PR), or complete response (CR). Patient was not considered bortezomib refractory. Bortezomib refractory is defined as no response on prior bortezomib-containing regimens or progression on or within 60 days of a bortezomib-containing regimen. |
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E.4 | Principal exclusion criteria |
A patient meeting any of the following criteria is not eligible to participate in the study: 1. Patient has had any prior allogeneic bone marrow transplant (patient with prior autologous transplant are eligible). 2. Patient plans to undergo any type of bone marrow transplantation (allogeneic, or autologous) within 4 weeks after initiating study therapy. 3. Patient has had prior treatment with vorinostat or HDAC inhibitors (e.g., depsipeptide, MS-275, LAQ-824, PXD-101, LBH589, MGCD0103, CRA024781, etc.). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not be enrolled in this study. (Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.) 4. Patient was unable to tolerate prior treatment with bortezomib. 5. Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: acute or chronic graft versus host disease, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within past 6 months, uncontrolled cardiac arrhythmia, renal failure, psychiatric or social conditions that may interfere with patient compliance, or any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the patient at unacceptable risk for adverse outcome if he/she were to participate in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for this study in PFS, the time from randomization to disease prgression or death due to any cause |
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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 | Yes |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 13 |
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 | No |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |