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Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia (HAPLO-EMPTY)

Primary Purpose

Refractory Idiopathic Aplastic Anemia, Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Allogenic transplantation
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Refractory Idiopathic Aplastic Anemia focused on measuring Acquired refractory idiopathic aplastic anemia, Haplo identical hematopoietic stem cell transplantation, Post-transplantation cyclophosphamide

Eligibility Criteria

3 Years - 35 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Aged from 3 to 35 years old
  • Suffering from refractory acquired idiopathic aplastic anemia (at least one course of immunosuppression with anti-thymocyte globulin)
  • Absence of geno-identical donor or 10/10 matched donor
  • With identification of a haploidentical donor (brother, sister, parents, adult children or cousin)
  • Absence of donor specific antibody detected in the patient with a MFI ≥ 1500 (antibodies directed towards the distinct haplotype between donor and recipient)

  • With usual criteria for HSCT :

    • ECOG(Eastern Cooperative Oncology Group) ≤ 2
    • No severe and uncontrolled infection
    • Cardiac function compatible with high dose of cyclophosphamide
  • Adequate organ function: ASAT(aspartate transaminase) and ALAT (alanine aminotransferase) ≤ 2.5 N (the norm), total bilirubin ≤ 2N, creatinine < 150 μmol/L
  • With health insurance coverage
  • Contraception methods must be prescribed during all the duration of the research. Women and men of childbearing age must use contraceptive methods within 12 months and 6 months after the last dose of cyclophosphamide, respectively.
  • Having signed a written informed consent (2 parents for patients aged less than 18)

Exclusion Criteria :

  • With no morphologic evidence of clonal evolution (patients with isolated bone marrow cytogenetic abnormalities are also eligible).
  • With uncontrolled infection
  • With seropositivity for HIV or HTLV-1 (Human T cell Leukemia) or active hepatitis B or C defined by a positive PCR (polymerase chain reaction) HBV (hepatitis B virus) or HCV (hepatitis C virus) and associated hepatic cytolysis
  • Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix)
  • Pregnant (βHCG positive) or breast-feeding.
  • Who received attenuated 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%
  • With heart failure according to NYHA (New York Heart Association) (II or more)
  • Preexisting acute hemorrhagic cystitis
  • Renal failure with creatinine clearance <30ml / min
  • With urinary tract obstruction
  • With contraindications to treatments used during the research
  • Who have any debilitating medical or psychiatric illness, which preclude understanding the inform consent as well as optimal treatment and follow-up
  • Under tutorship or curatorship

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Haploidentical allogeneic hematopoietic stem cell transplantation.

    Arm Description

    Conditioning regimen Fludarabine (30mg/m2/day i.v: day -6 to day -2), pre-transplant cyclophosphamide (14.5 mg/kg/day i.v: day -6 and day -5), and Total Body Irradiation (2 Gray on day-1) Stem cell source Bone Marrow GVHD Prophylaxis Rabbit ATG dosed at 0.5 mg/kg on day -9 and 2 mg/kg on days -8 and -7, Cyclophosphamide 50 mg/Kg/day at D+3 and D+4, Tacrolimus (residual 8-12 microg/L) and mycophenolate (MMF) from D+5. In absence of GvHD, MMF will be stopped at D35 and tacrolimus at day 365. Prevention of EBV reactivation Rituximab 150mg/m2 intravenously at Day+5 post HSCT, Each infusion of Rituximab will be preceded by administration of anti-pyretic and an antihistaminic, e.g. paracetamol and diphenhydramine.

    Outcomes

    Primary Outcome Measures

    Overall survival rate

    Secondary Outcome Measures

    Graft failure incidence
    Neutrophils engraftment
    3 consecutive days with neutrophiles >0.5 G/L
    Platelets engraftment
    7 consecutive days with platelets >20 G/L
    Absolute numbers of neutrophils
    Absolute numbers of neutrophils
    Absolute numbers of neutrophils
    Absolute numbers of neutrophils
    Absolute numbers of neutrophils
    Absolute numbers of neutrophils
    Absolute numbers of platelets
    Absolute numbers of platelets
    Absolute numbers of platelets
    Absolute numbers of platelets
    Absolute numbers of platelets
    Absolute numbers of platelets
    Incidence of use of growth factors for poor hematopoietic reconstitution
    Acute graft-versus-host disease (GvHD) incidence
    Chronic graft-versus-host disease (GvHD) incidence
    Relapse incidence
    Relapse incidence
    Progression free survival
    Progression free survival
    Incidence of cytomegalovirus (CMV) infection
    Incidence of Epstein-Barr virus (EBV) infection
    Severe infections (CTAE grade 3-4)
    Severe infections (CTAE grade 3-4)
    Severe infections (CTAE grade 3-4)
    Severe infections (CTAE grade 3-4)
    Non-relapse mortality
    Incidence of cardiac toxicities
    Overall survival
    Quality of life questionnaire for adults
    Quality of life will be assessed for adult using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ) " EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Quality of life questionnaire for minors
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Quality of life questionnaire for adults
    Quality of life will be assessed for adult using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Quality of life questionnaire for minors
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Quality of life questionnaire for adults
    Quality of life will be assessed for adults using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Quality of life questionnaire for minors
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Quality of life questionnaire for adults
    Quality of life will be assessed for adult using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Quality of life questionnaire for minors
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Proportion of patients with a donor chimerism of 90% or more
    Proportion of patients with a donor chimerism of 90% or more
    Proportion of patients with a donor chimerism of 90% or more
    Proportion of patients with a donor chimerism of 90% or more
    Proportion of patients with a donor chimerism of 90% or more
    Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
    Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
    Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Ferritin levels
    Ferritin levels
    Ferritin levels
    Ferritin levels

    Full Information

    First Posted
    October 15, 2021
    Last Updated
    November 8, 2021
    Sponsor
    Assistance Publique - Hôpitaux de Paris
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05126849
    Brief Title
    Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia
    Acronym
    HAPLO-EMPTY
    Official Title
    Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia: a Nationwide Phase II Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2021
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 25, 2021 (Anticipated)
    Primary Completion Date
    November 25, 2026 (Anticipated)
    Study Completion Date
    November 25, 2026 (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
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Outcomes for patients with severe aplastic anemia (SAA) who are refractory to first-line immunosuppressive therapy (IST) and who lack a matched unrelated donor (MUD) remain poor. Recently, the use of eltrombopag (ELT) has shown blood count improvements in 40% of these patients. However, most refractory patients do not respond to ELT or other second-line treatment and are therefore exposed to life-threatening infections, and bleeding. During the past 2 decades, there has been a significant decrease in infection-related mortality in patients with SAA unresponsive to initial IST but clonal evolution including paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML) still occur in the long-term with a grim prognosis. Overall, the overall survival of such patients with acquired refractory SAA to ELT is about 60-70% at 2 years. Hematopoietic stem cell transplantation (HSCT) using alternative donor sources (i.e., mismatched unrelated donors, cord blood (CBT), and haplo-identical family donors) may be curative in patients with refractory SAA, despite carrying much higher rates of complications than in transplantations from matched related or unrelated donors. Recently, our group showed that CBT is a valuable curative option for young adults with refractory SAA. However, not all patients have available CB and CBT treatment related mortality is high in adult patients. Haploidentical (haplo) related donor Stem Cell Transplantation (haplo-SCT) have improved dramatically outcomes using T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy). Preliminary results in a little number of patients with refractory SAA at Kings college (London, UK) and John Hopkins (Baltimore, USA) seem promising. The investigators retrospectively analyzed data from 36 patients (median age 42 years) transplanted between 2010 and 2017 in Europe on behalf of the SAA working party of the European Blood and Marrow Transplantation group. The 1-year overall survival was about 80% suggesting that this approach might be a valid option in this particular poor clinical situation. The main objective of this study is to demonstrate a benefit in term of the 2-year overall survival rate from 60% (historical rates in patients with acquired refractory idiopathic aplastic anemia) up to 80% using haplo-SCT with PTCy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Refractory Idiopathic Aplastic Anemia, Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation
    Keywords
    Acquired refractory idiopathic aplastic anemia, Haplo identical hematopoietic stem cell transplantation, Post-transplantation cyclophosphamide

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    31 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Haploidentical allogeneic hematopoietic stem cell transplantation.
    Arm Type
    Experimental
    Arm Description
    Conditioning regimen Fludarabine (30mg/m2/day i.v: day -6 to day -2), pre-transplant cyclophosphamide (14.5 mg/kg/day i.v: day -6 and day -5), and Total Body Irradiation (2 Gray on day-1) Stem cell source Bone Marrow GVHD Prophylaxis Rabbit ATG dosed at 0.5 mg/kg on day -9 and 2 mg/kg on days -8 and -7, Cyclophosphamide 50 mg/Kg/day at D+3 and D+4, Tacrolimus (residual 8-12 microg/L) and mycophenolate (MMF) from D+5. In absence of GvHD, MMF will be stopped at D35 and tacrolimus at day 365. Prevention of EBV reactivation Rituximab 150mg/m2 intravenously at Day+5 post HSCT, Each infusion of Rituximab will be preceded by administration of anti-pyretic and an antihistaminic, e.g. paracetamol and diphenhydramine.
    Intervention Type
    Other
    Intervention Name(s)
    Allogenic transplantation
    Intervention Description
    Conditioning regimen Fludarabine (30mg/m2/day i.v: day -6 to day -2), pre-transplant cyclophosphamide (14.5 mg/kg/day i.v: day -6 and day -5), and Total Body Irradiation (2 Gray on day-1) Stem cell source Bone Marrow GVHD Prophylaxis Rabbit ATG dosed at 0.5 mg/kg on day -9 and 2 mg/kg on days -8 and -7, Cyclophosphamide 50 mg/Kg/day at D+3 and D+4, Tacrolimus (residual 8-12 microg/L) and mycophenolate (MMF) from D+5. In absence of GvHD, MMF will be stopped at D35 and tacrolimus at day 365. Prevention of EBV reactivation Rituximab 150mg/m2 intravenously at Day+5 post HSCT, Each infusion of Rituximab will be preceded by administration of anti-pyretic and an antihistaminic, e.g. paracetamol and diphenhydramine.
    Primary Outcome Measure Information:
    Title
    Overall survival rate
    Time Frame
    at 2 years
    Secondary Outcome Measure Information:
    Title
    Graft failure incidence
    Time Frame
    at 2 years
    Title
    Neutrophils engraftment
    Description
    3 consecutive days with neutrophiles >0.5 G/L
    Time Frame
    at day 100
    Title
    Platelets engraftment
    Description
    7 consecutive days with platelets >20 G/L
    Time Frame
    at day 100
    Title
    Absolute numbers of neutrophils
    Time Frame
    at 1 month
    Title
    Absolute numbers of neutrophils
    Time Frame
    at 2 months
    Title
    Absolute numbers of neutrophils
    Time Frame
    at 3 months
    Title
    Absolute numbers of neutrophils
    Time Frame
    at 6 months
    Title
    Absolute numbers of neutrophils
    Time Frame
    at 12 months
    Title
    Absolute numbers of neutrophils
    Time Frame
    through study completion, an average of 6 months
    Title
    Absolute numbers of platelets
    Time Frame
    at 1 month
    Title
    Absolute numbers of platelets
    Time Frame
    at 2 months
    Title
    Absolute numbers of platelets
    Time Frame
    at 3 months
    Title
    Absolute numbers of platelets
    Time Frame
    at 6 months
    Title
    Absolute numbers of platelets
    Time Frame
    at 12 months
    Title
    Absolute numbers of platelets
    Time Frame
    through study completion, an average of 6 months
    Title
    Incidence of use of growth factors for poor hematopoietic reconstitution
    Time Frame
    up to one year
    Title
    Acute graft-versus-host disease (GvHD) incidence
    Time Frame
    at 3 months
    Title
    Chronic graft-versus-host disease (GvHD) incidence
    Time Frame
    at 24 months
    Title
    Relapse incidence
    Time Frame
    at 12 months
    Title
    Relapse incidence
    Time Frame
    at 24 months
    Title
    Progression free survival
    Time Frame
    at 12 months
    Title
    Progression free survival
    Time Frame
    at 24 months
    Title
    Incidence of cytomegalovirus (CMV) infection
    Time Frame
    at 12 months
    Title
    Incidence of Epstein-Barr virus (EBV) infection
    Time Frame
    at 12 months
    Title
    Severe infections (CTAE grade 3-4)
    Time Frame
    at 3 months
    Title
    Severe infections (CTAE grade 3-4)
    Time Frame
    at 6 months
    Title
    Severe infections (CTAE grade 3-4)
    Time Frame
    at 12 months
    Title
    Severe infections (CTAE grade 3-4)
    Time Frame
    at 24 months
    Title
    Non-relapse mortality
    Time Frame
    at 24 months
    Title
    Incidence of cardiac toxicities
    Time Frame
    at 12 months
    Title
    Overall survival
    Time Frame
    at 12 months
    Title
    Quality of life questionnaire for adults
    Description
    Quality of life will be assessed for adult using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ) " EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Time Frame
    at 3 months
    Title
    Quality of life questionnaire for minors
    Description
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Time Frame
    at 3 months
    Title
    Quality of life questionnaire for adults
    Description
    Quality of life will be assessed for adult using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Time Frame
    at 6 months
    Title
    Quality of life questionnaire for minors
    Description
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Time Frame
    at 6 months
    Title
    Quality of life questionnaire for adults
    Description
    Quality of life will be assessed for adults using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Time Frame
    at 12 months
    Title
    Quality of life questionnaire for minors
    Description
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Time Frame
    at 12 months
    Title
    Quality of life questionnaire for adults
    Description
    Quality of life will be assessed for adult using "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" EORTC QLQ-C30-V3 questionnaire.The QLQ-C30 is composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
    Time Frame
    at 24 months
    Title
    Quality of life questionnaire for minors
    Description
    Quality of life will be assessed for minor using The Pediatric Quality of Life Inventory™ (PedsQL™) The 36-item PedsQL™ Family Impact Module is a parent-report instrument designed to assess the impact of pediatric chronic health conditions on parents and the family. It includes 6 subscales measuring parents' self-reported functioning. The scale has five Likert response options, 'never', 'almost never', 'sometimes', 'often' and 'almost always' (corresponding to scores of 100, 75, 50, 25 and 0). Higher scores indicate better functioning.
    Time Frame
    at 24 months
    Title
    Proportion of patients with a donor chimerism of 90% or more
    Time Frame
    at 1 months
    Title
    Proportion of patients with a donor chimerism of 90% or more
    Time Frame
    at 3 months
    Title
    Proportion of patients with a donor chimerism of 90% or more
    Time Frame
    at 6 months
    Title
    Proportion of patients with a donor chimerism of 90% or more
    Time Frame
    at 12 months
    Title
    Proportion of patients with a donor chimerism of 90% or more
    Time Frame
    at 24 months
    Title
    Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
    Time Frame
    at 3 months
    Title
    Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
    Time Frame
    at 6 months
    Title
    Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
    Time Frame
    at 12 months
    Title
    Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
    Time Frame
    at 24 months
    Title
    Ferritin levels
    Time Frame
    at 3 months
    Title
    Ferritin levels
    Time Frame
    at 6 months
    Title
    Ferritin levels
    Time Frame
    at 12 months
    Title
    Ferritin levels
    Time Frame
    at 24 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    3 Years
    Maximum Age & Unit of Time
    35 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Aged from 3 to 35 years old Suffering from refractory acquired idiopathic aplastic anemia (at least one course of immunosuppression with anti-thymocyte globulin) Absence of geno-identical donor or 10/10 matched donor With identification of a haploidentical donor (brother, sister, parents, adult children or cousin) Absence of donor specific antibody detected in the patient with a MFI ≥ 1500 (antibodies directed towards the distinct haplotype between donor and recipient) With usual criteria for HSCT : ECOG(Eastern Cooperative Oncology Group) ≤ 2 No severe and uncontrolled infection Cardiac function compatible with high dose of cyclophosphamide Adequate organ function: ASAT(aspartate transaminase) and ALAT (alanine aminotransferase) ≤ 2.5 N (the norm), total bilirubin ≤ 2N, creatinine < 150 μmol/L With health insurance coverage Contraception methods must be prescribed during all the duration of the research. Women and men of childbearing age must use contraceptive methods within 12 months and 6 months after the last dose of cyclophosphamide, respectively. Having signed a written informed consent (2 parents for patients aged less than 18) Exclusion Criteria : With no morphologic evidence of clonal evolution (patients with isolated bone marrow cytogenetic abnormalities are also eligible). With uncontrolled infection With seropositivity for HIV or HTLV-1 (Human T cell Leukemia) or active hepatitis B or C defined by a positive PCR (polymerase chain reaction) HBV (hepatitis B virus) or HCV (hepatitis C virus) and associated hepatic cytolysis Cancer in the last 5 years (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix) Pregnant (βHCG positive) or breast-feeding. Who received attenuated 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% With heart failure according to NYHA (New York Heart Association) (II or more) Preexisting acute hemorrhagic cystitis Renal failure with creatinine clearance <30ml / min With urinary tract obstruction With contraindications to treatments used during the research Who have any debilitating medical or psychiatric illness, which preclude understanding the inform consent as well as optimal treatment and follow-up Under tutorship or curatorship
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Regis Peffault de Latour
    Phone
    +33142385073
    Email
    regis.peffaultdelatour@aphp.fr
    First Name & Middle Initial & Last Name or Official Title & Degree
    Matthieu Resche-Rigon
    Phone
    +33142499742
    Email
    matthieu.resche-rigon@u-paris.fr

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia

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