E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Steroid resistant grade II to IV acute graft-versus-host disease (GVHD) or poor graft function after allogeneic hematopoietic cell transplantation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10001756 |
E.1.2 | Term | Allogenic bone marrow transplantation therapy |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10045553 |
E.1.2 | Term | Unrelated donor bone marrow transplantation therapy |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018799 |
E.1.2 | Term | GVHD |
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 |
The present project aims at investigating the role of MSC for the treatment of patients with Part 1: Steroid-refractory grade II-IV acute GVHD, not eligible for, or not willing to participate to, the EBMT randomized protocol. Part 2: Poor graft function (PGF) Part 3: Low or falling donor T-cell chimerism after allogeneic HCT.
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E.2.2 | Secondary objectives of the trial |
1. Toxicity of MSC infusions 2. Incidence of acute (Appendix A) and chronic GVHD (Appendix B). 3. Overall and progression-free survival. 4. Incidence of bacterial, fungal and viral infections. 5. Disease progression or relapse. 6. Evidence of epithelial cells of MSC donor origin (assessed by STR-PCR) in bone marrow (and organs affected by GVHD : for part 1 only) after MSC infusion. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient eligibility criteria 1. Male or female of any age. 2. Previous allogeneic transplantation or autologous transplantation (for part 2 only) of HSC at any time before. 3. Informed consent given by donor or his/her guardian if of minor age. 4. Additional criteria for each part of the protocol: Part 1: MSC for steroid-refractory grade II-IV acute GVHD - Acute GVHD refractory to mPDN 2 mg/kg/day or equivalent Part 2: MSC for poor graft function (PGF) - Cytopenia in 2 or 3 lineages: - Cytopenia duration ≥ 2 weeks beyond day 28 after autologous HCT, or day 42 Part 3: MSC + DLI for poor donor T-cell chimerism - Nonmyeloablative allogeneic transplantation. - Donor T-cell chimerism < 50% for at least 2 consecutive weeks beyond day 21 after HCT OR ≥ 20% decrease in donor T-cell chimerism with the second value < 50%. |
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E.4 | Principal exclusion criteria |
1. HIV positive. 2. Active uncontrolled infection at time of scheduled MSC infusion. 3. Relapsing or progressing malignancy.
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E.5 End points |
E.5.1 | Primary end point(s) |
To establish efficacy of infusions of MSC from related HLA-identical, HLA-haploidentical or mismatched unrelated donors: Part 1: MSC for steroid-refractory grade II-IV acute GVHD : efficacy on steroid-resistant grade II - IV acute GVHD. Part 2: MSC for poor graft function (PGF) : efficacy on PGF. Part 3: MSC + DLI for poor donor T-cell chimerism after allogeneic HCT : efficacy on prevention of graft rejection in patients with low or failing donor T-cell chimerism after allogeneic HCT.
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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One year after the last patient will be included in the trial and be transplanted |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |