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 |
Multiple myeloma is a cancer of a type of white blood cell called plasma
cells. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
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 |
Comparison of perifosine to placebo with respect to progression‐free survival (PFS) in relapsed or relapsed/refractory multiple myeloma patients receiving bortezomib and dexamethasone. |
|
E.2.2 | Secondary objectives of the trial |
1) comparison perifosine to placebo with respect to an overall response
rate (ORR = partial response [PR] or better), overall survival (OS), and time to progression (TTP) in multiple myeloma patients receiving bortezomib and dexamethasone
2) Evaluation of the safety of the combination of perifosine, bortezomib, and dexamethasone compared to placebo, bortezomib, and dexamethasone. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with a confirmed diagnosis of relapsed or relapsed/refractory multiple myeloma that are currently progressing or have recently relapsed.
• Measurable disease (serum M‐protein >0.5g/dl and/or >200mg urinary M‐protein
excretion).
• Patients must have relapsed (progressed > 60 days) after their last dose of bortezomibbased therapy. In addition, patients may be refractory to (progressing on or within 60 days of discontinuing therapy) or relapsed from other non‐bortezomib‐based therapies.
• Patients must have previously received at least two cycles of either single agent
bortezomib treatment (21 day cycle) at the 1.3 mg/m2 dose or a minimum of 1.0 mg/m2 if used in combination with other active agents or in patients with underlying neuropathy.
• Patients must have previously received at least one cycle (minimum of 21 days) of an immunomodulatory agent (e.g. thalidomide, lenalidomide). There is no prior minimum dose requirement for a prior immunomodulatory agent.
• Patients must have received at least two anti‐myeloma therapies (which must include bortezomib and an immunomodulatory agent). Patients may have received one prior anti‐myeloma regimen which is required to contain a combination of bortezomib and an immunomodulatory agent. Therefore, patients must have received at least one and no more than four prior anti‐myeloma regimens and have progressive disease after the most recent treatment regimen. (Multiple lines of therapy may be most easily delineated by at least disease stabilization followed by a change in therapy due to progression).
• Patient must be willing and able to participate in PK sampling. |
|
E.4 | Principal exclusion criteria |
• Patients refractory to any regimen containing bortezomib.
• Patients with non‐secretory multiple myeloma. (myeloma where the malignant plasma cells do not secrete M protein or light chains).
• History of allergic reactions or intolerance attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine), bortezomib or dexamethasone or any of their components.
• Prior treatment with perifosine or an investigational proteasome inhibitor.
• Chemotherapy or other therapy experimental or proven that is or may be active against myeloma within two weeks (14 days) prior to Cycle 1 Day 1. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survial. The analysis, which is event‐based, will be conducted after approximately 265 randomized patients have progressed or died. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The analysis, which is event‐based, will be conducted after approximately 265 randomized patients have progressed or died. |
|
E.5.2 | Secondary end point(s) |
1. Comparison of perifosine to placebo with respect to an overall response rate (partial response [PR] or better), overall survival, and time to progression (TTP)
2. Evaluation of the safety of the combination of perifosine, bortezomib,
and dexamethasone compared to placebo, bortezomib, and dexamethasone. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The analysis, which is event‐based, will be conducted after approximately 265 randomized patients have progressed or died. |
|
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 | 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) | 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) | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Austria |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Ireland |
Israel |
Korea, Republic of |
Lithuania |
New Zealand |
Poland |
Russian Federation |
Slovakia |
South Africa |
Spain |
Ukraine |
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
|
The Core Phase is planned to continue until approximately 265 randomized patients have progressed or died.
Patients who are still alive and have not withdrawn consent when the study blind is broken may continue into the Extension Phase. If the primary efficacy results
demonstrate a benefit of perifosine, patients on placebo will be offered perifosine, and patients on perifosine will be entered into the Extension Phase and allowed to continue taking perifosine. |
|
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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |