Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant

Study Overview
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Brief Summary
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The primary objective of this study is to compare the 2-year progression free survival without acute graft versus host disease (GvHD) (aGvHD) grade III-IV or without moderate or severe chronic (cGVHD) after transplant from haploidentical hematopoietic stell cell transplant (HSCT) or from an unrelated Human Leukocyte Antigen (HLA)-9/10 mismatched unrelated donor (MMUD). It will use a Phase II, multicenter, prospective, randomized clinical trial. By setting a power of 80% and a type I error rate of 5% for a two-sided log-rank test (hypotheses tested: probability of event-free survival at 2 years 50% vs. 30 %), 92 patients need to be recruited in each arm, for a total of 184 patients.

Official Title
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Randomized Prospective Phase II Clinical Trial Using Post-Transplantation Cyclophosphamide for Prevention of GVHD in Haploidentical and HLA-9/10 Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant

Conditions
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Hematopoietic Stem Cell Transplant

Intervention / Treatment
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* Procedure: transplant from a haplo-identical donor
* Procedure: transplant from a non related donor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With a hematological malignancy requiring a HSCT and at least in partial response ie a) Acute Leukemia in complete remission, b) Myelodysplastic syndromes with less than 20% marrow, c) Myeloproliferative syndromes with less than 20% bone marrow blasts, d) Non Hodgkin Lymphoma (NHL), Hodgkin's disease, chronic lymphocytic leukemia at least in partial response, e) Myeloma at least in partial response. Without HLA matched related or unrelated donor Identification of a possible HLA-9/10 MMUD and a possible haplo-identical donor. Having read and understood the information letter and signed the informed consent With health insurance coverage Exclusion Criteria: Organic or psychiatric disease, non related to the hematological malignancy, contraindicating the transplant. Performance Scale by the Eastern Cooperative Oncology Group (ECOG)> 2 Severe uncontrolled infection Cardiac contraindication of post-transplant Cy (coronary insufficiency, ejection ventricular fraction <50%) Aspartate transaminase (AST) and alanine transaminase (ALT) > 2.5 N, creatinine > 150 mmol/L (except if related to malignancy) Previous active cancer in the last two years, except basal cell skin cancer and in situ carcinoma of the cervix Childbearing age woman refusing contraception Patients who did not accept the follow-up planned by the protocol Positive serology for HIV or Human T-Lymphotropic Virus (HTLV)-1, 2, or active viral infection by the Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Pregnant woman (positive β-HCG) or during lactation Adult patient on guardianship, or safeguard justice

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 55 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized prospective Phase II Clinical Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Haplo-identical group<br> | Procedure: transplant from a haplo-identical donor<br>* The transplant procedures will be similar in the 2 groups beside the origin of cells<br>|
| Active Comparator: HLA-9/10 MMUD group<br> | Procedure: transplant from a non related donor<br>* The transplant procedures will be similar in the 2 groups beside the origin of cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two-year progression free survival, without acute GVHD grade III-IV and without moderate/severe cGVHD |  | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 100 day engraftment |  | day 100 |