E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relpsed or refractory multiple myeloma |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the optimum dose of bendamustine when combined with thalidomide and dexamethasone (BTD) in the treatment of relapsed/refractory multiple myeloma, based on response rates, tolerability, and progression-free survival (PFS). |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• To determine maximum and overall response rates • To determine response duration • To determine time to next treatment • To determine safety and toxicity (particularly febrile neutropenia and septicaemia) • To determine longer term tolerability (ie the proportion of patients successfully receiving six cycles of treatment with bendamustine with not dose reductions or delays) • To assess the feasibility of stem cell harvest following treatment with bendamustine, thalidomide and dexamethasone (BTD) in eligible patients. • To determine overall survival
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males and females, aged ≥18 years • Histologically confirmed multiple myeloma (MM) with measurable disease parameters requiring therapy for relapsed or refractory disease (first relapse or later) • Women of child bearing potential and male patients whose partner is a woman of child bearing potential must be prepared to use effective methods of contraception in accordance with (and consent to) the Celgene and Astellas SPC-approved process for thalidomide and bendamustine risk management and pregnancy prevention, or commit to absolute and continuous abstinence. Men must not father a child for up to 6 months following cessation of treatment • Performance Status (ECOG) 0-3 • Life expectancy at least 3 months • Able to provide written informed consent
|
|
E.4 | Principal exclusion criteria |
• Pregnant or lactating. Women of child bearing potential must have a negative pregnancy test performed by a healthcare professional in accordance with the Celgene-approved process for thalidomide risk management and pregnancy prevention. • Non-secretory MM • Relapsed on previous bendamustine therapy • Unsupported platelet count <75 x 10 9/L within 14 days before enrolment (unless attributable to the myeloma in the opinion of the local investigator). • Absolute neutrophil count <1.5 x10 9/L within 14 days before enrolment. • Serum bilirubin >2 times upper limit of normal within 14 days before enrolment • Serum ALT/AST >2.5 times upper limit of normal within 14 days before enrolment • Calculated or measured creatinine clearance <10 mL/minute within 14 days before enrolment • ≥Grade 2 (NCI criteria) peripheral neuropathy within 14 days before enrolment. • Any history of hypersensitivity to any of the study medications or excipients • Seropositive for HIV, or active hepatitis A, B or C infection • Concurrent or previous malignancies (<12 months post end of treatment) at other sites, with the exception of appropriately treated localised epithelial skin or cervical cancer. Patients with histories (.≥12 months) of other tumours may be entered. • Evidence of clinically unstable disease, as determined by medical history, clinical laboratory tests, ECG results, and physical examination that, in the Investigator’s opinion, preclude entry into the study. • Poorly controlled hypertension or diabetes mellitus or other serious medical or psychiatric illness that, in the Investigator’s opinion, is likely to interfere with participation and/or compliance in this clinical study. • Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis. • Received an investigational medicinal product within 28 days of study entry (randomisation or registration) • Major surgery less than 30 days before start of treatment • Yellow fever vaccination within 3 month before enrolment
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
A joint primary outcome of the proportion of patients achieving at least a partial response (as defined by the Modified International Working Group (IWG) Uniform Response Criteria (Durie et al, 2006)) within six cycles of treatment, and the proportion of patients successfully able to receive both doses of bendamustine with no dose reductions and no more than a two week delay, is used to determine that each dosing schedule is sufficiently efficacious and tolerable to warrant further investigation.
The primary outcome measure of progression-free survival at 12 months post-randomisation is used to allow treatment selection should both dosing schedules be determined sufficiently efficacious and tolerable. |
|
E.5.2 | Secondary end point(s) |
• Maximum response rate and overall response rate • Response duration • Time to next treatment • Safety and toxicity • Proportion of patients successfully receiving six cycles of treatment with no dose reductions or delays • Feasibility of stem cell harvest following treatment • Overall survival
|
|
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 | No |
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 | 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 | Yes |
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 | 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 | No |
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 | 8 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 end of the trial is defined as the date of the last patient’s last treatment visit plus 28 days. Long term follow up for purposes of the Main REC and Research Governance to one month after the last patient’s last trial follow up visit constitutes the non-interventional phase of the trial. |
|
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 |