Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia or in Relapse After Immunosuppression
NCT ID: NCT05126849
Last Updated: 2023-11-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
31 participants
INTERVENTIONAL
2022-01-06
2027-01-06
Brief Summary
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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.
Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
OTHER
NONE
Study Groups
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Haploidentical allogeneic hematopoietic stem cell transplantation.
1. 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)
2. Stem cell source Bone Marrow
3. 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.
4. 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.
Allogenic transplantation
1. 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)
2. Stem cell source Bone Marrow
3. 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.
4. 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.
Interventions
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Allogenic transplantation
1. 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)
2. Stem cell source Bone Marrow
3. 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.
4. 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.
Eligibility Criteria
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Inclusion Criteria
* 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 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 live attenuated vaccine within 2 months before transplantation and during the research
* 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
* Who receive the following treatments Phenytoin, Pentostatin, inhibitor of adenoside)
* 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
3 Years
35 Years
ALL
No
Sponsors
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Assistance Publique - Hôpitaux de Paris
OTHER
Responsible Party
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Locations
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Crlcc Henri Becquerel Rouen
Rouen, , France
CHU Amiens
Amiens, , France
CHU Angers
Angers, , France
CHU Besancon
Besançon, , France
CHU Bordeaux
Bordeaux, , France
Hôpital du Haut-Lévêque
Bordeaux, , France
CHU Caen
Caen, , France
Hopital Percy
Clamart, , France
CHU Clermont
Clermont-Ferrand, , France
CHU-Estaing_Clermont Ferrand
Clermont-Ferrand, , France
Henri Mondor
Créteil, , France
CHU Grenoble
Grenoble, , France
CHU Lille
Lille, , France
CHU Lille
Lille, , France
CHU Limoges
Limoges, , France
CHU Lyon Sud
Lyon, , France
IHOP, CHU Lyon
Lyon, , France
Hopital La Timone
Marseille, , France
CHU Montpellier
Montpellier, , France
CHU Montpellier
Montpellier, , France
CHU Nancy
Nancy, , France
CHU Nantes
Nantes, , France
CHU Nantes
Nantes, , France
CHU Nice
Nice, , France
Hopital Necker
Paris, , France
Hopital Robert Debré
Paris, , France
Hôpital de La Pitié Salpetriere
Paris, , France
Hôpital Saint Antoine
Paris, , France
Hôpital Saint Louis
Paris, , France
CHU Poitiers
Poitiers, , France
CHU Rennes
Rennes, , France
CHU Rennes
Rennes, , France
ICLN_Saint Priest En Jarez
Saint-Priest-en-Jarez, , France
CHRU Strasbourg
Strasbourg, , France
CHU Toulouse
Toulouse, , France
Countries
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Central Contacts
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Facility Contacts
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Amandine Charbonnier
Role: primary
Sylvie Francois
Role: primary
Ana Berceanu
Role: primary
Charlotte Jubert
Role: primary
Edouard Forcade
Role: primary
Sylvain Chantepie
Role: primary
Johanna Konopacki
Role: primary
Olivier Bay Jacques
Role: primary
Justyna Kanold
Role: primary
Sébastien Maury
Role: primary
Claude-Eric Bulabois
Role: primary
Micha Srour
Role: primary
Bénédicte Bruno
Role: primary
Pascal Turlure
Role: primary
Fiorenza Barroco
Role: primary
Cécile Renard
Role: primary
Arthur Sterin
Role: primary
Patrice Ceballos
Role: primary
Anne Sirvent
Role: primary
Maud d'Aveni
Role: primary
Alice Garnier
Role: primary
Fanny Rialland
Role: primary
Michael Loschi
Role: primary
Felipe Suarez
Role: primary
Jean-Hugues Dalle
Role: primary
Stéphanie Nguyen Quoc
Role: primary
Mohamad Mohty
Role: primary
Natacha Maillard
Role: primary
Marc Bernard
Role: primary
Virginie Gandemer
Role: primary
Nathalie Contentin
Role: primary
Jérôme Cornillon
Role: primary
Bruno Lioure
Role: primary
Anne Huynh
Role: primary
Other Identifiers
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APHP200004
Identifier Type: -
Identifier Source: org_study_id