Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant

Hematopoietic Stem Cell Transplant Clinical Trial

— ALTERGREF  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03250546
• Other study ID #: P151001
• Status: Recruiting
• Phase: Phase 2
• Start date: November 20, 2017
• Est. completion date: November 30, 2022

Study information

• Verified date: February 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 184
• Est. completion date: November 30, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 55 Years

Eligibility

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 ß-HCG) or during lactation

• Adult patient on guardianship, or safeguard justice

Related Conditions & MeSH terms

• Hematopoietic Stem Cell Transplant

Intervention

Procedure:
• transplant from a haplo-identical donor
The transplant procedures will be similar in the 2 groups beside the origin of cells
• transplant from a non related donor
The transplant procedures will be similar in the 2 groups beside the origin of cells

Locations

Country	Name	City	State
France	Saint Louis hospital	Paris
France	Service Hématologie Clinique	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall survival		2 year
Other	Progression Free survival		2 year
Other	Cumulative incidence of progression		2 year
Other	Acute GVHD incidence		day 100
Other	Chronic GVHD incidence		2 year
Other	Non relapse Mortality (NRM)		year 2
Other	Stages of Chimerism	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.	month 1, 2, 3, 6 and 12
Other	Severe infections		2 year
Other	Time interval between diagnosis and transplant		day 100
Other	Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	day 100 and two years
Primary	Two-year progression free survival, without acute GVHD grade III-IV and without moderate/severe cGVHD		2 year
Secondary	100 day engraftment		day 100