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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 100000004864 |
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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 |
To evaluate the effect of Lenalidomide given after reduced intensity conditioned stem cell transplant on progression-free survival at 2 years in myeloma |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of adjuvant Lenalidomide use early after reduced intensity conditioned transplantation
To define the potential benefit of combining Lenalidomide with a reduced intensity allograft
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria • Multiple myeloma subjects who have received a high dose melphalan conditioned autologous transplant in the preceding 180 days and who are in CR1 or VGPR1 after their first line of treatment or CR2 or VGPR2 after treatment of first relapse. CR/VGPR are as defined by International uniform response criteria for Myeloma, 2006 (appendix 1). VGPR for non-secretory myeloma is not defined in this criteria. For this study VGPR in non-secretory myeloma patients is defined as a 90% reduction in plasma cells, provided there were 30% or more plasma cells at diagnosis. • Patients >18 years and ≤70 years in whom allogeneic transplantation using a reduced intensity conditioning regimen is not contra-indicated but who are not suitable for conventional allograft • ECOG status 2 or an ECOG status of 3 if the reason for a status of 3 is due exclusively to multiple myeloma (e.g. pathological fracture) (Appendix 2) • Patients with a HLA identical related or ten/ten antigen (A,B,C,DQ,DR) matched unrelated donor • Cardiac ejection fraction > 40%. Or report stating left ventricular function is satisfcatory or normal • Creatinine clearance >50 ml/min • Liver function (AST or ALT) < 2.5 x upper limit of normal • Patients able to give written informed consent prior to allogeneic transplant, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice • Patients willing and able to comply with the protocol for the duration of the study • Agree to abstain from donating blood (and semen in male subjects) while taking study drug therapy and for 28 days following discontinuation of study drug therapy • Agree not to share study drug with another person and to return all unused study drug to the investigator or pharmacist
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E.4 | Principal exclusion criteria |
• Patients with allergies or contraindications to receiving fludarabine, Lenalidomide, ciclosporin or ATG • Patients with a known positive serology for HIV/Hepatitis B/Hepatitis C • Patients who have undergone a previous allogeneic stem cell transplant • Patients who have previously progressed on Lenalidomide • Pregnant or lactating women • Adults of reproductive potential not willing to comply with the Lenalidomide Risk Minimisation Plan (see below for details) • Patients with organ allografts • Any co-morbidity that, in the investigators opinion, would affect the patient’s participation in this study • Patients who have taken any other investigational medical product within 4 weeks of starting conditioning therapy
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival at 2 years post entry into the trial |
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E.5.2 | Secondary end point(s) |
• Progression Free Survival at 3 years post-transplantation • Disease Free Survival at 3 years post-transplantation • Toxicity profile of adjunctive Lenalidomide based on CTCAE criteria • Tolerability of adjunctive Lenalidomide • Response to RIC transplantation in combination with adjunctive Lenalidomide defined by the International uniform response criteria for multiple myeloma (Appendix 1)at 3 years post-transplantation • Donor engraftment based on linage-specific chimerism at 2 years post-transplantation • Day +100 and 1 year non-relapse mortality rates • Graft Versus Host Disease based on Glucksberg criteria • Overall survival at 1, 2 and 3 years post-transplant • Second primary malignancy incidence at 3 years post-transplant • Further treatment requirements |
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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 | 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 | No |
E.8.1.2 | Open | No |
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 | No |
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 | 9 |
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
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The end of the trial will be 6 months after the last visit of the last patient. This will allow sufficient time for the completion of protocol procedures, data collection and data input. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 29 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 31 |