Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-versus-host Disease

Study Overview
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Brief Summary
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Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning from HLA-mismatched PBSC or cord blood: a Pilot Study

Official Title
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Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning: a Pilot Study

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Procedure: Mesenchymal stem cell infusion


Participation Criteria
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Eligibility Criteria
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V.1. Patients V.1.1. Diseases Hematological malignancies confirmed histologically and not rapidly progressing: AML in CR; ALL in CR; CML unresponsive/intolerant to Imatinib but not in blast crisis; Other myeloproliferative disorders not in blast crisis and not with extensive myelofibrosis; MDS with < 5% blasts; Multiple myeloma; CLL; Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease); Hodgkin's disease. V.1.2. Clinical situations Theoretical indication for a standard allo-transplant, but not feasible because: Age > 55 yrs; Unacceptable end organ performance; Patient's refusal. Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant. V.1.3. Other inclusion criteria Male or female; fertile female patients must use a reliable contraception method; Age < 75 yrs. Informed consent given by patient or his/her guardian if of minor age. V.1.4. Exclusion criteria Any condition not fulfilling inclusion criteria; HIV positive; Terminal organ failure, except for renal failure (dialysis acceptable); Uncontrolled infection, arrhythmia or hypertension; Previous radiation therapy precluding the use of 2 Gy TBI; HLA-identical donor. V.2. PBSC donors V.2.1. Inclusion criteria Related to the recipient (sibling, parent or child) or unrelated; Male or female; Weight > 15 Kg (because of leukapheresis); Fulfills generally accepted criteria for allogeneic PBSC donation; Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures. V.2.2. Exclusion criteria Any condition not fulfilling inclusion criteria; HIV positive; Unable to undergo leukapheresis because of poor vein access or other reasons. V.2.3. HLA matching Related or unrelated donors who have 1-2 HLA mismatches, as either : One antigenic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1 One allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1 Two allelic mismatches at HLA-A or -B or -C or -DRB1 or -DQB1 One antigenic mismatch + 1 allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1. One antigenic mismatch at -DQB1 and one other antigenic mismatch at HLA-A or -B or -C or -DRB1 V.3. Cord blood unit Banked cord blood units will be used if they fulfill the following criteria: No more than 2/6 HLA mismatches (antigenic mismatch at HLA-A or HLA-B or allelic mismatch at HLA-DRB1) > 2.5 x 107 TNC/kg Standard validation by FACT/Netcord criteria.

Ages Eligible for Study
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Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>MSC co-infusion with either HLA-mismatched PBSC or cord blood | Procedure: Mesenchymal stem cell infusion<br>* Infusion of mesenchymal stem cells on the same day as hematopoietic stem cell infusion.<br>* Other names: Mesenchymal stem cells;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day-100 incidence of non-relapse mortality |  | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1. Hematopoietic engraftment and graft rejection. 2. Incidence of grade II-IV and III-IV acute GVHD. 3. Immunologic reconstitution |  | 365 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCT, nonmyeloablative, mesenchymal stem cells, GVHD