E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Allogeneic transplantation for patients with multiple myeloma |
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E.1.1.1 | Medical condition in easily understood language |
Patient with multiple myeloma receives bone marrow or peripheral blood stem cells from another person.
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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 | LLT |
E.1.2 | Classification code | 10059041 |
E.1.2 | Term | Allogeneic peripheral haematopoietic stem cell transplant |
E.1.2 | System Organ Class | 100000004865 |
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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 | 10018651 |
E.1.2 | Term | Graft versus host disease |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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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 |
For the phase II trial on patients with multiple myeloma: Evaluate the toxicity of the maintenance with bortezomib and lenalidomide |
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E.2.2 | Secondary objectives of the trial |
For the phase II trial on patients with multiple myeloma:
· Analyze the response and relapse rate of this approach
· Evaluate the toxicity of the procedure in terms of acute and chronic GVHD and mortality
· Evaluate the toxicity of the procedure
· Evaluate the efficacy of VRD in terms of improvement of disease response
· Evaluate the efficacy of the procedure in terms of event free and overall survival
· Analyze the prognostic value and efficacy of imaging studies using PET and local radiotherapy in involved fields prior to or after (> 100 days) conditioning |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria for the phase II trial:
o High-risk multiple myeloma patients at first relapse / second complete remission candidates to receive an allogeneic transplantation
o Age: ³ 18 < 70 years.
o Suitable donor, related or unrelated (a maximum of 1 mismatched is allowed)
o Measurable disease
o High risk first relapse is defined as:
· First early relapse after ASCT (< 24 months)
· First late relapses in case the patient does not achieve CR after second ASCT
· First relapse in patients with poor cytogenetic features
o All subjects must be able to comply with the Lenalidomide Pregnancy Prevention
o Patient signs the study informed consent form |
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E.4 | Principal exclusion criteria |
- Patient who is a known carrier of the human immunodeficiency virus (HIV), hepatitis B virus surface antigen or active infection by the hepatitis C virus (those in which the hepatitis C virus RNA can be detected).
- Patients who have experienced a myocardial infarction within 6 months prior to entry in the clinical trial or are in New York Heart Association (NYHA) functional class III or IV, heart failure, uncontrolled angina, uncontrolled ventricular arrhythmia or acute ischemia detected in the ECG, or conduction system abnormalities.
- Patients who are currently in another clinical trial or receiving any investigational agent
- Prior history of other malignant diseases other than myeloma (except for basal or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) unless the patient is disease-free longer than 5 years.
- Hypertension or poorly-controlled diabetes mellitus or any other serious organic disease involving an excessive risk to the patient or any psychiatric disorder that interferes with the understanding of the informed consent
o Prior severe comorbidity such as:
Cirhosis
· Peripheral neuropathy ³ Grade 2 14 days prior to inclusion
· Psychiatric disease
· Hypersensitivity to Bz, Boric acid manitol.
· Patients unable to use appropriate contraceptive methods
· Patients who have received an investigational drug 30 days prior to inclusion
· Patients with pericardial disease
· Patients with acute diffuse infiltrative pulmonary
· Patients not willing to comply with the Lenalidomide Pregnancy Prevention Risk Management Plan
· Patients not willing to receive thromboprophylaxis during the consolidation phase will not be eligible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
For the phase I trial:
Safety, assessed as toxicity and incidence of GVHD, of the combination sirolimus plus Bz for GVHD prophylaxis in patients with hematologic malignancies undergoing allogeneic transplantation
For the phase II trial:
Safety and efficacy of an optimized strategy of allogeneic transplantation among patients with multiple myeloma |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety evaluation will be performed every 5 patients in order to analyze the tolerability and feasibility of the approach. Once confirmed we will also analyze the impact of this approach on the efficacy of the procedure in terms of response and relapse rate. |
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E.5.2 | Secondary end point(s) |
- Response and relapse rate
- Toxicity
- Improvement of disease response
- Event free and overall survival
- Prognostic value and efficacy of imaging studies using PET and local radiotherapy in involved fields prior to or after conditioning |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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.8.2.4 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |