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

Primary Purpose

Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myeloproliferative Syndromes

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Haplo donor stem cell transplantation
HLA 10/10 MUD stem cell transplantation
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

15 Years - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Haploidentical donor stem cell transplantation

    HLA 10/10 MUD stem cell transplantation

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    Time interval between indication of stem cell transplantation (SCT) and transplant
    Engraftment
    Engraftment: at least 3 consecutive days with neutrophils > 0.5 G/L, with platelets > 20 G/L
    Numbers of neutrophils
    Absolute numbers of neutrophils
    Numbers of platelets
    Absolute numbers of platelets
    Numbers of neutrophils
    Absolute numbers of neutrophils
    Numbers of platelets
    Absolute numbers of platelets
    Numbers of neutrophils
    Absolute numbers of neutrophils
    Numbers of platelets
    Absolute numbers of platelets
    Numbers of neutrophils
    Absolute numbers of neutrophils
    Numbers of platelets
    Absolute numbers of platelets
    Numbers of neutrophils
    Absolute numbers of neutrophils
    Numbers of platelets
    Absolute numbers of platelets
    Numbers of neutrophils
    Absolute numbers of neutrophils
    Numbers of platelets
    Absolute numbers of platelets
    Use of growth factors
    Use of growth factors for poor hematopoietic reconstitution
    Immune reconstitution
    Immune reconstitution by analyzing T, B, Natural Killer (NK), regulatory T cell levels in the peripheral blood
    Immune reconstitution
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Immune reconstitution
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Immune reconstitution
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Immune reconstitution
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Iron overload estimation
    Iron overload estimation
    Iron overload estimation
    Iron overload estimation
    Iron overload estimation
    Chimerism
    Chimerism
    Chimerism
    Chimerism
    Acute GvHD
    Incidence of acute GvHD
    First line treatment
    Response to steroids
    Treatment courses for refractory aGVHD
    Relapse
    Incidence of relapse
    Progression free survival
    Severe infections (CTAE grade 3-4)
    Cytomegalovirus (CMV)
    Incidence of CMV
    Epstein-Barr virus (EBV)
    Incidence of EBV reactivation
    Veno-occlusive disease (VOD)
    Incidence of veno-occlusive disease
    Severity of veno-occlusive disease (VOD)
    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
    Incidence of cardiac toxicities
    Non-relapse mortality
    Overall survival
    Time between death and inclusion
    Quality of life post transplantation: EORTC QLQ-C30- v3
    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
    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 6 months: EORTC QLQ-C30- v3
    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 12 months: EORTC QLQ-C30- v3
    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 24 months: EORTC QLQ-C30- v3
    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.
    Number of new days of hospitalization after the hospitalization for transplantation

    Full Information

    First Posted
    June 6, 2018
    Last Updated
    August 30, 2018
    Sponsor
    Assistance Publique - Hôpitaux de Paris
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03655145
    Brief Title
    HLA 10/10 Matched Unrelated Donor vs Haploidentical Allogenic Hematopoietic Stem Cell Transplantation
    Acronym
    MacHaploMud
    Official Title
    Randomized Prospective Phase III Clinical Trial Comparing HLA 10/10 Matched Unrelated Donor and Haploidentical Allogenic Hematopoietic Stem Cell Transplantation After Myeloablative Conditioning Regimen
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2018
    Overall Recruitment Status
    Unknown status
    Study Start Date
    August 2018 (Anticipated)
    Primary Completion Date
    June 2019 (Anticipated)
    Study Completion Date
    June 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Assistance Publique - Hôpitaux de Paris

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    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.
    Detailed Description
    An unrelated adult donor who is HLA-matched to the recipient at the allele-level (at HLA-A, -B, -C, -DQB1 and -DRB1) is considered the best choice in the absence of an HLA-matched sibling for patients needing hematopoietic stem cell transplantation (SCT). However, using matched unrelated donors (MUD) is limited by (1) a prolonged time to identify and schedule donation for some MUD allowing some patients to relapse before transplantation can be performed, and (2) limited availability of fully HLA-MUD for the non-Caucasian population. Alternative donors are used for transplantation in patients without a fully-MUD including single HLA mismatched unrelated donor, unrelated umbilical cord blood and grafts from haploidentical related donors but are associated with higher non-relapse mortality and delayed immune reconstitution. A more recent strategy for haploidentical (haplo) related donor SCT (haplo-SCT) has improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy). From retrospective studies, haplo-SCT with PTCy are associated with similar overall and progression-free survivals as with MUD stem cell transplantation (MUD-SCT), but with lower rates of toxicity and graft versus host disease (GvHD), and thus potentially better results than MUD-SCT after reduced intensity conditioning (RIC) regimen. Haplo-SCT with PTCy is thus highly discussed nowadays motivating prospective trials to confirm the benefit of this procedure. In the setting of a myeloablative conditioning (MAC) regimen in adults with high risk hematological malignancies, few retrospective non-controlled registry studies recently suggest that outcomes after haplo-SCT using PTCy approach might also be superior in terms of GVHD free survival to that after MUD stem cell transplantation (MUD-SCT). The investigators propose to address this question, in a randomized prospective phase III clinical trial comparing HLA 10/10 MUD and haplo-SCT after MAC regimen. The stem cell source will be bone marrow for haploidentical SCT and peripheral blood stem cell (PBSC) for HLA-matched unrelated transplantation. The primary endpoint is the 1-year progression free survival without acute grade II-IV GvHD and without moderate and severe chronic GvHD.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myeloproliferative Syndromes, Myelodysplastic Syndromes

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    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
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    344 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Haploidentical donor stem cell transplantation
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    HLA 10/10 MUD stem cell transplantation
    Arm Type
    Active Comparator
    Arm Description
    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 Type
    Other
    Intervention Name(s)
    Haplo donor stem cell transplantation
    Intervention Description
    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.
    Intervention Type
    Other
    Intervention Name(s)
    HLA 10/10 MUD stem cell transplantation
    Intervention Description
    HLA 10/10 matched unrelated donor myeloablative transplantation
    Primary Outcome Measure Information:
    Title
    Progression free survival, without acute grade II-IV GvHD and without moderate and severe chronic GvHD.
    Description
    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.
    Time Frame
    12 months
    Secondary Outcome Measure Information:
    Title
    Time interval between indication of stem cell transplantation (SCT) and transplant
    Time Frame
    24 months
    Title
    Engraftment
    Description
    Engraftment: at least 3 consecutive days with neutrophils > 0.5 G/L, with platelets > 20 G/L
    Time Frame
    at 24 months
    Title
    Numbers of neutrophils
    Description
    Absolute numbers of neutrophils
    Time Frame
    at 1 month
    Title
    Numbers of platelets
    Description
    Absolute numbers of platelets
    Time Frame
    at 1 month
    Title
    Numbers of neutrophils
    Description
    Absolute numbers of neutrophils
    Time Frame
    at 2 months
    Title
    Numbers of platelets
    Description
    Absolute numbers of platelets
    Time Frame
    at 2 months
    Title
    Numbers of neutrophils
    Description
    Absolute numbers of neutrophils
    Time Frame
    at 3 months
    Title
    Numbers of platelets
    Description
    Absolute numbers of platelets
    Time Frame
    at 3 months
    Title
    Numbers of neutrophils
    Description
    Absolute numbers of neutrophils
    Time Frame
    at 6 months
    Title
    Numbers of platelets
    Description
    Absolute numbers of platelets
    Time Frame
    at 6 months
    Title
    Numbers of neutrophils
    Description
    Absolute numbers of neutrophils
    Time Frame
    at 12 months
    Title
    Numbers of platelets
    Description
    Absolute numbers of platelets
    Time Frame
    at 12 months
    Title
    Numbers of neutrophils
    Description
    Absolute numbers of neutrophils
    Time Frame
    at 24 months
    Title
    Numbers of platelets
    Description
    Absolute numbers of platelets
    Time Frame
    at 24 months
    Title
    Use of growth factors
    Description
    Use of growth factors for poor hematopoietic reconstitution
    Time Frame
    at 12 months
    Title
    Immune reconstitution
    Description
    Immune reconstitution by analyzing T, B, Natural Killer (NK), regulatory T cell levels in the peripheral blood
    Time Frame
    at 1 month post transplantation
    Title
    Immune reconstitution
    Description
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Time Frame
    at 3 months post transplantation
    Title
    Immune reconstitution
    Description
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Time Frame
    at 6 months post transplantation
    Title
    Immune reconstitution
    Description
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Time Frame
    at 12 months post transplantation
    Title
    Immune reconstitution
    Description
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Time Frame
    at 24 months post transplantation
    Title
    Iron overload estimation
    Time Frame
    at 1 month
    Title
    Iron overload estimation
    Time Frame
    at 3 months
    Title
    Iron overload estimation
    Time Frame
    at 6 months
    Title
    Iron overload estimation
    Time Frame
    at 12 months
    Title
    Iron overload estimation
    Time Frame
    at 24 months
    Title
    Chimerism
    Time Frame
    at 1 month
    Title
    Chimerism
    Time Frame
    at 3 months
    Title
    Chimerism
    Time Frame
    at 6 months
    Title
    Chimerism
    Time Frame
    at 12 months
    Title
    Acute GvHD
    Description
    Incidence of acute GvHD
    Time Frame
    at 24 months
    Title
    First line treatment
    Time Frame
    24 months
    Title
    Response to steroids
    Time Frame
    24 months
    Title
    Treatment courses for refractory aGVHD
    Time Frame
    24 months
    Title
    Relapse
    Description
    Incidence of relapse
    Time Frame
    24 months
    Title
    Progression free survival
    Time Frame
    24 months
    Title
    Severe infections (CTAE grade 3-4)
    Time Frame
    12 months
    Title
    Cytomegalovirus (CMV)
    Description
    Incidence of CMV
    Time Frame
    12 months
    Title
    Epstein-Barr virus (EBV)
    Description
    Incidence of EBV reactivation
    Time Frame
    12 months
    Title
    Veno-occlusive disease (VOD)
    Description
    Incidence of veno-occlusive disease
    Time Frame
    3 months
    Title
    Severity of veno-occlusive disease (VOD)
    Description
    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.
    Time Frame
    3 months
    Title
    Cardiac toxicities
    Description
    Incidence of cardiac toxicities
    Time Frame
    12 months
    Title
    Non-relapse mortality
    Time Frame
    12 months
    Title
    Overall survival
    Description
    Time between death and inclusion
    Time Frame
    24 months
    Title
    Quality of life post transplantation: EORTC QLQ-C30- v3
    Description
    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.
    Time Frame
    1 week post-transplantation
    Title
    Quality of life at 3 months: EORTC QLQ-C30- v3
    Description
    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.
    Time Frame
    3 months
    Title
    Quality of life at 6 months: EORTC QLQ-C30- v3
    Description
    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.
    Time Frame
    6 months
    Title
    Quality of life at 12 months: EORTC QLQ-C30- v3
    Description
    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.
    Time Frame
    12 months
    Title
    Quality of life at 24 months: EORTC QLQ-C30- v3
    Description
    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.
    Time Frame
    24 months
    Title
    Number of new days of hospitalization after the hospitalization for transplantation
    Time Frame
    at 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    15 Years
    Maximum Age & Unit of Time
    55 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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) Exclusion Criteria: 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Régis Peffault de Latour
    Phone
    +33142385073
    Email
    regis.peffaultdelatour@aphp.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sylvie Chevret
    Phone
    +33142499742
    Email
    sylvie.chevret@paris7.jussieu.fr

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

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

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