Multi Donor Mismatched Stem Cell Transplantation (MDT)

Study Overview
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Brief Summary
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The proposed research focuses on the development of innovative protocol of mismatched stem cell transplantation with combined 2 different haplo stem cell transplantation (SCT) donors which are mismatched to the recipient (and preferably to each other), in a patient in need for SCT, lacking an HLA match related or an unrelated donor. This innovative protocol named multi donor stem cell transplantation (MDT) is designed to facilitate engraftment even when reduced intensity conditioning or a low cell dose are used, improve the graft vs. leukemia (GVL) effect and enhance immune reconstitution (using quantitative and qualitative parameters).

Official Title
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Enhancement of Hematopoietic Stem Cell Engraftment by Multi Donor Stem Cell Transplantation (MDT) From 2 Mismatched Donors, a Phase I-II Open Study

Conditions
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Graft-Versus-Host Disease

Intervention / Treatment
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* Procedure: Multi donor stem cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patient age 0-70 years old with leukemia in 1st remission at high risk of relapse because of unfavorable prognostic features, at 2nd CR or MDS without an readily available matched donor (related or unrelated). Patients must have a mismatched donor willing and capable of donating peripheral blood stem cells and/or bone marrow progenitor cells using conventional techniques, and lymphocytes if indicated (mismatched defined as 3/6-4/6 HLA matching). Each patient / patient's guardian must sign written informed consent. Patients must have an ECOG PS ≤ 2; Creatinine <2.0 mg/dl; Ejection fraction >40%; DLCO >50% of predicted; Serum bilirubin <3 gm/dl; elevated GPT or GOT <3 x normal values. Exclusion criteria: Not fulfilling any of the inclusion criteria. Not in CR (if the indication for transplant is leukemia). Active life-threatening infection. Overt untreated infection. HIV seropositivity, Hepatitis B or C antigen positivity with evidence of active hepatitis. Pregnant or lactating women. Donor contraindication (HIV seropositive confirmed by Western Blot, Hepatitis B antigenemia, HCV, evidence of bone marrow disease, unable to donate bone marrow or peripheral blood due to concurrent medical condition). Previous autologous or allogeneic stem cell transplantation. Inability to comply with study requirements.

Ages Eligible for Study
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Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment<br> | Procedure: Multi donor stem cell transplantation<br>* stem cell transplantation from 2 donors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day of neutrophil engraftment |  | 30d | 
| Day of platelet engraftment>20x10(9)L |  | 30 | 
| Acute GVHD occurrence>2 |  | 100d | 
| Disease free survival |  | 100d | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Day of platelet engraftment>50x10(9)/L |  | 30d | 
| Time of acute GVHD |  | 100d | 
| GVHD grade |  | 100d | 
| Overall survival |  | 100 days | 
| Infections incidence |  | 100d | 
| transplant-related mortality |  | 100d | 
| Transplant related toxicity |  | 100d | 
| Immune reconstitution |  | 100d | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cell transplantation, GVHD