Haploidentical and Mismatched Unrelated Donors Hematopoietic Stem Cell Transplant (ALTERGREF)

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.

Study Overview

• Status: Unknown
• Conditions: Hematopoietic Stem Cell Transplant
• Intervention / Treatment: Procedure: transplant from a haplo-identical donor; Procedure: transplant from a non related donor

• Study Type: Interventional
• Enrollment (Anticipated): 184
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Saint Louis Hospital
    • Contact: Nathalie DHEDIN, MD; Phone Number: 33+142385127; Email: nathalie.dhedin@aphp.fr
    • Principal Investigator: Nathalie Dhedin, MD
  • Paris, France, 75013
    • Recruiting
    • Service Hématologie Clinique
    • Contact: Stéphanie NGUYEN, MD PhD; Phone Number: 33+142162823; Email: stephanie.nguyen-quoc@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	Time Frame
100 day engraftment	day 100

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival		2 year
Progression Free survival		2 year
Cumulative incidence of progression		2 year
Acute GVHD incidence		day 100
Chronic GVHD incidence		2 year
Non relapse Mortality (NRM)		year 2
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
Severe infections		2 year
Time interval between diagnosis and transplant		day 100
Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	day 100 and two years

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2017
• Primary Completion (Anticipated): November 30, 2022
• Study Completion (Anticipated): November 30, 2022

Study Registration Dates

• First Submitted: July 31, 2017
• First Submitted That Met QC Criteria: August 14, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 18, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: P151001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No