E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with hematological malignancies not candidate for conventional allogeneic transplantation because of age or comorbidities. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027703 |
E.1.2 | Term | Mismatched donor bone marrow transplantation therapy |
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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 mesenchymal stem cells (MSC) for the prevention of graft rejection and graft-versus-host disease (GVHD) after allogeneic HCT with nonmyeloablative conditioning in patients receiving either HLA-mismatched peripheral blood stem cells (PBSC) from related or unrelated donors or banked cord blood. This is a non-randomized phase I-II study examining the feasibility and toxicity of this approach, and obtaining preliminary efficacy data for a later phase III study. Further, we will investigate, in vitro, the ability of MSC (the same as infused to the patient) to block/mitigate the induction of recipient skin explant GVHD by donor T-cells. |
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E.2.2 | Secondary objectives of the trial |
1. To examine hematopoietic (whole blood and T cell chimerism) engraftment and to evaluate the incidence of graft rejection. 2. To evaluate the incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD). 3. To investigate the quality and timing of immunologic reconstitution. 4. To detect MSC of MSC donor origin in recipient marrow after HCT. 5. To assess the impact of MSC on skin GVHD in vitro in the skin explant model.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient 1. Hematological malignancies confirmed histologically and not rapidly progressing. 2. Theoretical indication for a standard allo-transplant, but not feasible because: Age > 55 yrs; Unacceptable end organ performance; Patient’s refusal. OR Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant. 3. Male or female; fertile female patients must use a reliable contraception method; 4 Age <or = 75 yrs. 5 Informed consent given by patient or his/her guardian if of minor age. 6 HLA-compatibility with HSC or cord blood donor as described in the protocol
Donor 1 Related to the recipient (sibling, parent or child) or unrelated; 2 Fulfills generally accepted criteria for allogeneic PBSC donation; 3 Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.
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E.4 | Principal exclusion criteria |
Patient 1 Any condition not fulfilling inclusion criteria; 2 HIV positive; 3 Terminal organ failure, except for renal failure (dialysis acceptable); 4 Uncontrolled infection, arrhythmia or hypertension; 5 Previous radiation therapy precluding the use of 2 Gy TBI; 6 HLA-identical donor.
Donor
1 Any condition not fulfilling inclusion criteria; 2 HIV positive; 3 Unable to undergo leukapheresis because of poor vein access or other reasons.
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E.5 End points |
E.5.1 | Primary end point(s) |
To study the feasibility and safety (defined as a day-100 incidence of non-relapse mortality < 35%) of allogeneic hematopoietic transplantation following nonmyeloablative conditioning with co-infusion of mesenchymal stem cells and HLA-mismatched hematopoietic stem cells. |
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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 | 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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | 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 | 3 |
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 | 3 |