E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Cancer of plasma cells (white blood cells) |
|
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) |
|
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 define the objective response rate associated with the administration of vorinostat in combination with bortezomib to patients with relapsed or 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 enalidomide). |
|
E.2.2 | Secondary objectives of the trial |
To assess the tolerability and adverse experience profile of vorinostat administered in combination with bortezomib.
To assess the time to disease progression associated with the administration of vorinostat in combination with bortezomib.
To evaluate the progression-free survival associated with the administration of vorinostat in combination with bortezomib.
To evaluate overall survival associated with the administration of vorinostat in combination with bortezomib.
|
|
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 myeloma diagnostic criteria.
2. Patient has relapsed and refractory multiple myeloma after at least 2 prior treatment regimens as per the EBMT response criteria 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).
3. Patient has measurable disease, defined as any quantifiable serum M-protein value and/or, where applicable, urine M-protein of ≥200 mg/24 hours
4. Patient has received at least 2 prior (standard or experimental) anti-myeloma regimens.
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 (patients 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 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.
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 endpoint for this study is response rate, defined as the percentage of subjects who achieve partial response or better during the study. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
When at least 29 patients have achieved partial response or better
(defined by EBMT criteria) |
|
E.5.2 | Secondary end point(s) |
-Time to Progression (TTP): defined as the time from allocation to the first documented disease progression or death due to myeloma.
-Progression-free survival (PFS): defined as the time from allocation to
the first documented disease progression or death due to any cause, whichever
occurs first.
-Overall survival: defined as the time from allocation to death due to any cause.
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. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
When 142 patients have disease progression or discontinue from
progression assessments |
|
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 |
|
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 | 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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
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 | 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 |
Australia |
Belgium |
Canada |
France |
Germany |
Greece |
Israel |
Italy |
Korea, Republic of |
Russian Federation |
Spain |
United Kingdom |
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
|
When 142 patients have been enrolled and the last enrolled patient has completed Cycle 8 of therapy. |
|
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 | 5 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |