E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Symptomatic Multiple Myeloma after first-line autologous stem cell transplantation |
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E.1.1.1 | Medical condition in easily understood language |
Symptomatic Multiple Myeloma after first-line autologous stem cell transplantation |
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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 | 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 |
Immunotherapy with autologous messenger RNA-electroporated monocyte derived dendritic cells in combination with lenalidomide maintenance will induce significant anti-tumor cellular immune responses in multiple myeloma patients achieving very good partial response or complete response after autologous stem cell transplantation. This will result in an improvement in response quality which will eventually lead to improved progression-free and overall survival. |
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E.2.2 | Secondary objectives of the trial |
1.To demonstrate the in-vivo immunogenicity of autologous MAGE-A3 and MAGE-C1 mRNA-electroporated monocyte derived dendritic cell vaccinations in combination with lenalidomide maintenance as evaluated by : -Ex-vivo functional analysis including the demonstration of specific anti-MAGE-A3 and MAGE-C1 T cell immunoreactivity. -In-vivo delayed type hypersensitivity response assessment with MAGE-A3 and MAGE-C1 protein. 2.To determine progression-free survival and overall survival (OS). 3.Assessment of safety and toxicity of lenalidomide maintenance and dendritic cell vaccination. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For the standard primary treatment phase: 1.Able and willing to give valid written informed consent (IC1) before additional blood and bone marrow samples are collected. 2.Patients must have newly diagnosed symptomatic multiple myeloma. 3.Measurable disease. 4.Age at diagnosis : 18- 65 years. 5.Eligible for autologous stem cell transplantation. 6.Collection of adequate bone-marrow samples to construct patient-specific PCR probes for minimal residual disease analysis
For leukapheresis: 1.Able and willing to give valid written informed consent (IC2) before leukapheresis. 2.Having reached at least partial remission after autolous stem cell transplantation.
For the experimental treatment phase: 1.Able and willing to give valid informed consent (IC3) before the start of the experimental treatment 2.At least in complete remission or very good partial response after autologous stem cell transplantation with or without consolidation 3.Eastern Cooperative Oncology Group performance status of 0 or 1
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E.4 | Principal exclusion criteria |
EXCLUSION CRITERIA FOR STANDARD TREATMENT PHASE Patients will be excluded for enrolment if they fulfil any of the following criteria: 1.Multiple myeloma of IgM subtype 2.POEMS syndrome 3.Plasma cell leukaemia or circulating plasma cells > 2 x 10E9/L. 4.Waldenstrom’s macroglobulinemia 5.Patients with known amyloidosis 6.HIV, HbsAg or hepatitis C serology positivity 7.History of other malignancy (other than basal cell carcinoma and carcinoma of the cervix in situ) 8.Significant neuropathy (grades 3 to 4, or grade 2 with pain) within 14 days prior to start standard treatment phase. 9.Female patients who are pregnant or lactating. 10.Any other clinically significant medical disease or psychiatric condition that, in the investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent.
EXCLUSION CRITERIA FOR EXPERIMENTAL TREATMENT PHASE 1.Concomitant chemotherapy or other antimyeloma treatment 2.Concomitant immunosuppressive drugs including glucocorticosteroids 3.Any other clinically significant medical disease or psychiatric condition that, in the investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate a significant improvement in the response quality after dendritic cell vaccination in combination with lenalidomide maintenance. Improvement in response quality is defined as : -Achieving complete response after dendritic cells vaccination for patients in very good partial response before vaccination. -Achieving a minimal residual disease negative state after dendritic cell vaccination for patients with complete remission having minimal residual disease positive state before vaccination. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuously during the conduct of the trial |
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E.5.2 | Secondary end point(s) |
1.To demonstrate the in-vivo immunogenicity of autologous MAGE-A3 and MAGE-C1 mRNA-electroporated monocyte derived dendritic cell vaccinations in combination with lenalidomide maintenance as evaluated by : -Ex-vivo functional analysis including the demonstration of specific anti-MAGE-A3 and MAGE-C1 T cell immunoreactivity. -In-vivo delayed type hypersensitivity response assessment with MAGE-A3 and MAGE-C1 protein. 2.To determine progression-free survival and overall survival (OS). 3.Assessment of safety and toxicity of lenalidomide maintenance and dendritic cell vaccination. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuously during the conduct of the trial |
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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 | Yes |
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 | 3 |
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 study will occur at the time point when the last patient included in the experimental phase of the study will be off study either due to progression or due to unacceptable toxicity or withdrawal of patient’s consent. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |