HLA 10/10 Matched Unrelated Donor vs Haploidentical Allogenic Hematopoietic Stem Cell Transplantation

NCT03655145 | Unknown Phase 3

• 1 other identifier: AOM 17030
• Study Type: interventional
• Target: 344
• Locations: 0 countries
• Sites: N/A

Brief Summary

The MAC-HAPLO-MUD trial is a randomized prospective phase III trial comparing HLA 10/10 matched unrelated donor and haploidentical allogeneic hematopoietic stem cell transplantation after myeloablative conditioning regimen in patients, age 15 years or older, with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) or Myeloproliferative Syndrome (SMP) or Myelodysplastic Syndromes (SMD) and requiring allogeneic hematopoietic stem cell transplantation. Primary endpoint is the 1-year progression free survival without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Myeloproliferative Syndromes; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Progression free survival, without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

  One year progression free survival, without acute grade II-IV GvHD and without moderate and severe chronic GvHD. -Relapse evaluation: For myeloid malignancies, the relapse will be defined by the reappearance of leukemic cells after SCT. For ALL, the relapse will be defined by: the reappearance of leukemic cells after SCT and/or an increase of at least 50 % of the smallest measure of any lymphnode considered abnormal in the pre-transplantation period for patients in partial response and in non-responders and/or the appearance of any new lesion in comparison with the pre-transplantation period evaluation. \- GvHD evaluation: Grading of acute GVHD will be performed according to the classification of Glusckberg. Grading of chronic GVHD will be performed according to the NIH classification.

  12 months

Secondary Outcomes (49)

• Time interval between indication of stem cell transplantation (SCT) and transplant

  24 months

• Engraftment

  at 24 months

• Numbers of neutrophils

  at 1 month

• Numbers of platelets

  at 1 month

• Numbers of neutrophils

  at 2 months

Study Arms (2)

Haploidentical donor stem cell transplantation

EXPERIMENTAL

The stem cell source will be bone marrow for haploidentical transplantation.The bone marrow collection is carried out according to the practice of each centre with a minimal target dose of 3x108 TNC/kg.

Other: Haplo donor stem cell transplantation

HLA 10/10 MUD stem cell transplantation

ACTIVE COMPARATOR

The stem cell source will be peripheral blood stem cell for HLA-matched unrelated transplantation.Peripheral blood stem cell (PBSC) for HLA-matched unrelated SCT will be mobilized by G-CSF (Neupogen®) administered to the donor from Day-4 to Day-1 subcutaneously (10µg/kg/day) with the minimal target dose of 4.106 CD34+ cells/kg.

Other: HLA 10/10 MUD stem cell transplantation

Interventions

Haplo donor stem cell transplantation OTHER

The algorithm for selection of haploidentical donor has been defined by the french society for stem cell transplantation The stem cell source will be bone marrow for haploidentical transplantation.The bone marrow collection is carried out according to the practice of each centre with a minimal target dose of 3x108 TNC/kg.

Haploidentical donor stem cell transplantation

HLA 10/10 MUD stem cell transplantation OTHER

HLA 10/10 matched unrelated donor myeloablative transplantation

HLA 10/10 MUD stem cell transplantation

Eligibility Criteria

• Age: 15 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• With AML/ALL/SMD/SMP requiring allogeneic stem cell transplantation
• In complete response (CR) for AML/ALL or in CR, or partial response (PR) or non pre-treated for SMD/SMP \*
• Without a HLA matched related donor available
• With a good probability to have a HLA-10/10 matched donor available (the patient needs to have at least 5 MUD identified within the book "BMDW (Bone Marrow Donors Worldwide)"
• With identification of a haploidentical donor (brother, sister, parents, adult children or cousin)
• Absence of donor specific antibody (DSA) detected in the patient with a MFI ≥ 2000 (antibodies directed towards the distinct haplotype between donor and recipient)
• With usual criteria for hematopoietic stem cell transplant (HSCT):
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• No severe and uncontrolled infection
• Cardiac function compatible with high dose of cyclophosphamide
• Adequate organ function: aspartate transaminase (ASAT) and alanine aminotransferase (ALAT) ≤ 2N, total bilirubin ≤ 1.5N, creatinine clearance ≥30ml/min (except if those abnormalities are linked to the hematological disease)
• With health insurance coverage
• Understand informed consent or optimal treatment and follow-up
• Contraception methods must be prescribed during all the duration of the research and using effective contraceptive methods during treatment and within 12 months for women and 6 months for men after the last dose of cyclophosphamide
• Having signed a written informed consent (2 parents for patients aged less than 18)

You may not qualify if:

• Presence of donor specific antibody (DSA) with a MFI ≥ 2000 detected in the patient
• History of Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix)
• Uncontrolled infection
• Seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive polymerase chain reaction (PCR) hepatitis B virus (HBV) or hepatitis C virus (HCV) and hepatic cytolysis due to HBV
• Yellow fever vaccine within 2 months before transplantation
• Uncontrolled coronary insufficiency, recent myocardial infarction \<6 month, current manifestations of heart failure, uncontrolled cardiac rhythm disorders, ventricular ejection fraction \<50%
• Heart failure according to New York Heart Association (NYHA) (II or more)
• Urinary tract obstruction
• Contraindications to treatments used during the research
• Preexisting acute hemorrhagic cystitis
• Renal failure with creatinine clearance \<30ml / min
• Pregnancy ( β- human chorionic gonadotropin (β-HCG positive)) or breast-feeding
• Any debilitating medical or psychiatric illness which would preclude the realization of the SCT or the understanding of the protocol
• Under protection by law (tutorship or curatorship)
• Unwilling or unable to comply with the protocol

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Central Study Contacts

Régis Peffault de Latour

CONTACT

+33142385073; regis.peffaultdelatour@aphp.fr

Sylvie Chevret

CONTACT

+33142499742; sylvie.chevret@paris7.jussieu.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized prospective Phase III clinical trial comparing HLA 10/10 matched unrelated donor (standard arm) and haploidentical allogeneic hematopoietic stem cell transplantation (experimental arm) after myeloablative conditioning regimen

Study Record Dates

• First Submitted: June 6, 2018
• First Posted: August 31, 2018
• Study Start: August 1, 2018
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2023
• Last Updated: August 31, 2018

Record last verified: 2018-05