Hematopoietic Stem Cell Transplant
Conditions
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.
Interventions
PROCEDUREtransplant from a haplo-identical donor
The transplant procedures will be similar in the 2 groups beside the origin of cells
PROCEDUREtransplant from a non related donor
The transplant procedures will be similar in the 2 groups beside the origin of cells
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized prospective Phase II Clinical Trial
Eligibility
Sex/Gender
ALL
Age
15 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Two-year progression free survival, without acute GVHD grade III-IV and without moderate/severe cGVHD | 2 year |
Secondary
| Measure | Time frame |
|---|---|
| 100 day engraftment | day 100 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of progression | 2 year | — |
| Acute GVHD incidence | day 100 | — |
| Chronic GVHD incidence | 2 year | — |
| Non relapse Mortality (NRM) | year 2 | — |
| Overall survival | 2 year | — |
| Severe infections | 2 year | — |
| Time interval between diagnosis and transplant | day 100 | — |
| Adverse events | day 100 and two years | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
| Stages of Chimerism | month 1, 2, 3, 6 and 12 | * Complete chimerism: 100% donor cells detected, suggesting complete hematopoietic replacement * Mixed chimerism: Host cells are detected in particular cells like lymphocytes. Five to 90% donor cells * Split chimerism: One or more lineages are of host and one or more lineages are of donor, like myeloid cells are 100% host and T-cells are 100% donor. |
| Progression Free survival | 2 year | — |
Countries
France
Outcome results
None listed