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 |
Objective: To define the objective response rate associated with the administration of vorinostat in combination with bortezomib to patients with relapsed and refractory multiple myeloma after at least 2 prior treatment regimens, who meet both of the following conditions: Refractory to Bortezomib (administered either alone or in combination with other agents); defined as no response on prior bortezomib-containing regimens or progression on or within 60 days of a bortezomib-containing regimen. Relapsed, refractory, intolerant, and/or ineligible (in the opinion of the Investigator) to other therapies, including an IMiD (thalidomide OR lenalidomide). Hypothesis: Administration of vorinostat in combination with bortezomib will result in a clinically meaningful rate of objective response. |
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E.2.2 | Secondary objectives of the trial |
Secondary 1) Objective: To assess the tolerability and adverse experience profile of vorinostat administered in combination with bortezomib. 2) Objective: To assess the time to disease progression associated with the administration of vorinostat in combination with bortezomib. 3) Objective: To evaluate the progression-free survival associated with the administration of vorinostat in combination with bortezomib. 4) Objective: To evaluate overall survival associated with the administration of vorinostat in combination with bortezomib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
SUBJECT/PATIENT 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 myeloma diagnostic criteria located in Appendix 6.5 [10; 11]. 4. Patient has relapsed and refractory multiple myeloma after at least 2 prior treatment regimens as per the EBMT response criteria located in Appendix 6.6 [12] and meets both of the following conditions: Refractory to Bortezomib (administered either alone or in combination with other agents); defined as no response on prior bortezomib-containing regimens or progression on or within 60 days of a bortezomib-containing regimen. Relapsed, refractory, intolerant, and/or ineligible (in the opinion of the Investigator) to other therapies, including an IMiD (thalidomide OR lenalidomide). 5. Patient must have performance status of ≤ 2 on the ECOG Performance Scale located in Appendix 6.7 [13]. 6. Patient has measurable disease, defined as any quantifiable serum M-protein value and, where applicable, urine light chain of ≥200 mg/24 hours. 7. Female patient of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of study drug. 8. Female patient of childbearing potential is willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study, starting with Visit 1 through 30 days after the last dose of study drug. Adequate contraceptive methods include for example, intra-uterine device, diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide. Spermicides alone are not an acceptable method of contraception. |
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E.4 | Principal exclusion criteria |
SUBJECT/PATIENT 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 is eligible). 2. Patient plans to undergo any type of bone marrow transplantation (allogeneic, or autologous) within 4 weeks after initiating study therapy. 3. Patient had prior treatment with vorinostat or other 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. |
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E.5 End points |
E.5.1 | Primary end point(s) | |
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 | No |
E.6.5 | Efficacy | No |
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | No |
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) | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |