Etude : MAC-HAPLO-MUD / MAC-HAPLO-MUD



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : MAC-HAPLO-MUD

Nom : MAC-HAPLO-MUD

Traitement :

Type d'étude : Hors ciblage moléculaire

Dernière MÀJ : 03/09/2019
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Randomized Prospective Phase III Clinical Trial Comparing HLA 10/10 Matched Unrelated Donor and Haploidentical Allogenic Hematopoietic Stem Cell Transplantation After Myeloablative Conditioning Regimen

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C92 - Leucémie myéloïde

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C91 - Leucémie lymphoïde

Spécialité : Tissus lymphoïde, hématopoïétique et apparentés
Localisation : C88 - Maladies immunoprolifératives malignes
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : 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.

Study arms:
- Experimental: Haploidentical donor 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.
Intervention: Other: Haplo donor stem cell transplantation
- Active Comparator: HLA 10/10 MUD stem cell transplantation
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.
Intervention: Other: HLA 10/10 MUD stem cell transplantation

Current primary outcome:
Progression free survival, without acute grade II-IV GvHD and without moderate and severe chronic GvHD. [ Time Frame: 12 months ]
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.

Current secondary outcomes:
- Time interval between indication of stem cell transplantation (SCT) and transplant [ Time Frame: 24 months ]
- Engraftment [ Time Frame: at 24 months ]: Engraftment: at least 3 consecutive days with neutrophils > 0.5 G/L, with platelets > 20 G/L
- Numbers of neutrophils [ Time Frame: at 1 month ]: Absolute numbers of neutrophils
- Numbers of platelets [ Time Frame: at 1 month ]: Absolute numbers of platelets
- Numbers of neutrophils [ Time Frame: at 2 months ]: Absolute numbers of neutrophils
- Numbers of platelets [ Time Frame: at 2 months ]: Absolute numbers of platelets
- Numbers of neutrophils [ Time Frame: at 3 months ]: Absolute numbers of neutrophils
- Numbers of platelets [ Time Frame: at 3 months ]: Absolute numbers of platelets
- Numbers of neutrophils [ Time Frame: at 6 months ]: Absolute numbers of neutrophils
- Numbers of platelets [ Time Frame: at 6 months ]: Absolute numbers of platelets
- Numbers of neutrophils [ Time Frame: at 12 months ]: Absolute numbers of neutrophils
- Numbers of platelets [ Time Frame: at 12 months ]: Absolute numbers of platelets
- Numbers of neutrophils [ Time Frame: at 24 months ]: Absolute numbers of neutrophils
- Numbers of platelets [ Time Frame: at 24 months ]: Absolute numbers of platelets
- Use of growth factors [ Time Frame: at 12 months ]: Use of growth factors for poor hematopoietic reconstitution
- Immune reconstitution [ Time Frame: at 1 month post transplantation ]: Immune reconstitution by analyzing T, B, Natural Killer (NK), regulatory T cell levels in the peripheral blood
- Immune reconstitution [ Time Frame: at 3 months post transplantation ]: Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
- Immune reconstitution [ Time Frame: at 6 months post transplantation ]: Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
- Immune reconstitution [ Time Frame: at 12 months post transplantation ]: Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
- Immune reconstitution [ Time Frame: at 24 months post transplantation ]: Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
- Iron overload estimation [ Time Frame: at 1 month ]
- Iron overload estimation [ Time Frame: at 3 months ]
- Iron overload estimation [ Time Frame: at 6 months ]
- Iron overload estimation [ Time Frame: at 12 months ]
- Iron overload estimation [ Time Frame: at 24 months ]
- Chimerism [ Time Frame: at 1 month ]
- Chimerism [ Time Frame: at 3 months ]
- Chimerism [ Time Frame: at 6 months ]
- Chimerism [ Time Frame: at 12 months ]
- Acute GvHD [ Time Frame: at 24 months ]: Incidence of acute GvHD
- First line treatment [ Time Frame: 24 months ]
- Response to steroids [ Time Frame: 24 months ]
- Treatment courses for refractory aGVHD [ Time Frame: 24 months ]
- Relapse [ Time Frame: 24 months ]: Incidence of relapse
- Progression free survival [ Time Frame: 24 months ]
- Severe infections (CTAE grade 3-4) [ Time Frame: 12 months ]
- Cytomegalovirus (CMV) [ Time Frame: 12 months ]: Incidence of CMV
- Epstein-Barr virus (EBV) [ Time Frame: 12 months ]: Incidence of EBV reactivation
- Veno-occlusive disease (VOD) [ Time Frame: 3 months ]: Incidence of veno-occlusive disease
- Severity of veno-occlusive disease (VOD) [ Time Frame: 3 months ]: Severity of veno-occlusive disease. VOD severity will be assessed using new EBMT criteria (Mohty et al., 2016). EBMT criteria for grading VOD severity in adult patients are based on the level of bilirubin and its rate of change, liver function (transaminase), weight increase, renal function and the kinetic of their onset (Mohty et al., 2016). This grading system is divided into five categories as following: mild, moderate; severe, very severe; and death. Mohty M., Malard F., Abecassis M., Aerts E., Alaskar AS. et al. (2016). Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplantation 51,906-912.
- Cardiac toxicities [ Time Frame: 12 months ]: Incidence of cardiac toxicities
- Non-relapse mortality [ Time Frame: 12 months ]
- Overall survival [ Time Frame: 24 months ]: Time between death and inclusion
- Quality of life post transplantation: EORTC QLQ-C30- v3 [ Time Frame: 1 week post-transplantation ]
Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems. EORTC QLQ-C30 Scoring Manual. Fayers PM et al. on behalf of the EORTC Quality of Life Group. EORTC, 2001. ISBN: 2-9300.
- Quality of life at 3 months: EORTC QLQ-C30- v3 [ Time Frame: 3 months ]
- Quality of life at 6 months: EORTC QLQ-C30- v3 [ Time Frame: 6 months ]
- Quality of life at 12 months: EORTC QLQ-C30- v3 [ Time Frame: 12 months ]
- Quality of life at 24 months: EORTC QLQ-C30- v3 [ Time Frame: 24 months ]
- Number of new days of hospitalization after the hospitalization for transplantation [ Time Frame: at 24 months ]

Phase : III

Stade : NA

NA
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - 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)

Critères de non-inclusion : - 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
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT03655145
Promoteur :
APHP
Type de sponsor : Institutionnel
75010 PARIS 10

Coordonnateur :
Professeur régis PEFFAUT DE LA TOUR
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Ibrahim YAKOUB-AGHA

TEC / ARC / IDE :
Secrétariat de recherche
fanny.miquel@
chru-lille.fr
03.20.44.57.13

Ouverture de l'essai : OUVERT

MAJ : 21/05/2019