Clinical trial NCT03250546: Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hematopoietic Stem Cell Transplant
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2017-08-15
Enrollment: 184
Sex: ALL
Minimum age (years): 15
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized prospective Phase II Clinical Trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Two-year progression free survival, without acute GVHD grade III-IV and without moderate/severe cGVHD
timeFrame: 2 year
Secondary outcomes:
measure: 100 day engraftment
timeFrame: day 100
Other outcomes:
measure: Overall survival
timeFrame: 2 year
measure: Progression Free survival
timeFrame: 2 year
measure: Cumulative incidence of progression
timeFrame: 2 year
measure: Acute GVHD incidence
timeFrame: day 100
measure: Chronic GVHD incidence
timeFrame: 2 year
measure: Non relapse Mortality (NRM)
timeFrame: year 2
measure: Stages of Chimerism
timeFrame: month 1, 2, 3, 6 and 12
measure: Severe infections
timeFrame: 2 year
measure: Time interval between diagnosis and transplant
timeFrame: day 100
measure: Adverse events
timeFrame: day 100 and two years
Locations:
city: Paris
country: France
facility: Saint Louis hospital
city: Paris
country: France
facility: Service Hématologie Clinique
Study officials:
References: