Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant

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

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.

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