E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of plasma cells (white blood cells) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 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. |
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E.2.2 | Secondary objectives of the trial |
•To assess the tolerability of vorinostat administered in combination with bortezomib
•To determine the OS of patients with multiple myeloma, after at least 1 prior treatment regimen, treated with bortezomib and vorinostat compared to patients treated with bortezomib and placebo
•To determine the TTP 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
•To determine the objective RR of patients with multiple myeloma, after at least 1 prior treatment regimen, treated with bortezomib and vorinostat compared to patients treated with bortezomib and placebo using the European Blood and Marrow Transplant Group (EBMT) Criteria
•To measure pharmacokinetic parameters and conduct pharmacokinetic/ pharmacodynamic modeling to explore exposure/response relationships in patients treated with bortezomib together with vorinostat compared to bortezomib together with placebo
|
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient has an established diagnosis of multiple myeloma based on the myeloma diagnostic criteria.
2. 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.
3. For any patient who received prior bortezomib-containing regimen the
patient must also meet the following criteria:
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.
4. Patient has measurable disease, defined as any quantifiable serum Mprotein
value and/or, where applicable, urine M-protein of ≥200 mg/24 hours.
5. Patient has adequate organ function.
A full list of inclusion criteria can be found in the protocol. |
|
E.4 | Principal exclusion criteria |
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 is receiving corticosteroid therapy (>10 mg of prednisone or
equivalent). However, use of ≤10 mg of prednisone or equivalent is allowed for reasons other than myeloma.
A full list of exclusion criteria can be found in the protocol. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint for this study is PFS, the time from randomization to disease progression or death due to any cause. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 412 confirmed documented disease progressions and deaths have
been observed |
|
E.5.2 | Secondary end point(s) |
Overall survival: defined as the time from randomization to death due to any cause.
Time to Progression (TTP): defined as the time from randomization to the first
documented disease progression or death due to myeloma
Objective response rate: defined as the proportion of patients in the analysis population who have complete response (CR), partial response (PR) or
minimal response (MR) during the course of the study as determined by the IAC.
Safety endpoints:
-The number of patients with Grade 3-5 adverse experiences
-Duration, intensity, and time to onset of toxicities
-Adverse experiences, laboratory safety assessments, ECOG, ECGs, and vital signs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 412 confirmed
documented disease progressions and deaths have been observed |
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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 |
Patient Reported Outcomes |
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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.8.2.4 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Brazil |
Canada |
China |
Croatia |
Hong Kong |
India |
Israel |
Korea, Republic of |
Malaysia |
Mexico |
New Zealand |
Philippines |
Russian Federation |
South Africa |
Taiwan |
Thailand |
United States |
|
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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As defined in the protocol |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |