Refractory Idiopathic Aplastic AnemiaPhase 2HAPLO-EMPTYNCT05126849
Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia or in Relapse After Immunosuppression
A Phase 2 study testing Allogenic transplantation in people with Refractory Idiopathic Aplastic Anemia and Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation, run by Assistance Publique - Hôpitaux de Paris at 35 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 35 years
- Conditions the study is for
- Refractory Idiopathic Aplastic Anemia, Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation
- What is being tested?
- Allogenic transplantation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 35 sitesFrance
- Study dates
- 6 Jan 2022to 6 Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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 :
Show all 13Show fewer
- 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)
Who cannot join
- With morphologic evidence of clonal evolution (patients with isolated bone marrow cytogenetic abnormalities are also eligible excepted chromosome 7 abnormalities and complex karyotype)
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
35 sites in 1 country. Contact the study team or a site near you to ask about taking part.
35 sites in 1 country
France35 sites, 35 recruiting
- Recruiting
CHU Amiens
Amiens
Amandine Charbonnier
- Recruiting
CHU Angers
Angers
Sylvie Francois
- Recruiting
CHU Besancon
Besançon
Ana Berceanu
- Recruiting
CHU Bordeaux
Bordeaux
Charlotte Jubert
- Recruiting
Hôpital du Haut-Lévêque
Bordeaux
Edouard Forcade
- Recruiting
CHU Caen
Caen
Sylvain Chantepie
- Recruiting
Hopital Percy
Clamart
Johanna Konopacki
- Recruiting
CHU Clermont
Clermont-Ferrand
Olivier Bay Jacques
- Recruiting
CHU-Estaing_Clermont Ferrand
Clermont-Ferrand
Justyna Kanold
- Recruiting
Henri Mondor
Créteil
Sébastien Maury
- Recruiting
CHU Grenoble
Grenoble
Claude-Eric Bulabois
- Recruiting
CHU Lille
Lille
Micha Srour
- Recruiting
CHU Lille
Lille
Bénédicte Bruno
- Recruiting
CHU Limoges
Limoges
Pascal Turlure
- Recruiting
CHU Lyon Sud
Lyon
Fiorenza Barroco
- Recruiting
IHOP, CHU Lyon
Lyon
Cécile Renard
- Recruiting
Hopital La Timone
Marseille
Arthur Sterin
- Recruiting
CHU Montpellier
Montpellier
Patrice Ceballos
- Recruiting
CHU Montpellier
Montpellier
Anne Sirvent
- Recruiting
CHU Nancy
Nancy
Maud d'Aveni
- Recruiting
CHU Nantes
Nantes
Alice Garnier
- Recruiting
CHU Nantes
Nantes
Fanny Rialland
- Recruiting
CHU Nice
Nice
Michael Loschi
- Recruiting
Hopital Necker
Paris
Felipe Suarez
- Recruiting
Hopital Robert Debré
Paris
Jean-Hugues Dalle
- Recruiting
Hôpital de La Pitié Salpetriere
Paris
Stéphanie Nguyen Quoc
- Recruiting
Hôpital Saint Antoine
Paris
Mohamad Mohty
- Recruiting
Hôpital Saint Louis
Paris
Régis Peffault de Latour, +33142385073, regis.peffaultdelatour@aphp.fr
- Recruiting
CHU Poitiers
Poitiers
Natacha Maillard
- Recruiting
CHU Rennes
Rennes
Marc Bernard
- Recruiting
CHU Rennes
Rennes
Virginie Gandemer
- Recruiting
Crlcc Henri Becquerel Rouen
Rouen
Nathalie Contentin
- Recruiting
ICLN_Saint Priest En Jarez
Saint-Priest-en-Jarez
Jérôme Cornillon
- Recruiting
CHRU Strasbourg
Strasbourg
Bruno Lioure
- Recruiting
CHU Toulouse
Toulouse
Anne Huynh
About this study
Official title: Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia or in Relapse After Immunosuppression: a Nationwide Phase II Study
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.
- Conditions
- Refractory Idiopathic Aplastic Anemia, Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation
- Being tested
- Allogenic transplantation
- Keywords
- Acquired refractory idiopathic aplastic anemia, Haplo identical hematopoietic stem cell transplantation, Post-transplantation cyclophosphamide
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogenic transplantationOther
- 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.
| Study group | Role | What they receive |
|---|---|---|
| Haploidentical allogeneic hematopoietic stem cell transplantation. | Experimental | 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. Receives: Other: Allogenic transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival rate
Measured: at 2 years
Secondary outcomes (52)
Graft failure incidence
Measured: at 2 years
Neutrophils engraftment
3 consecutive days with neutrophiles >0.5 G/L
Measured: at day 100
Platelets engraftment
7 consecutive days with platelets >20 G/L
Measured: at day 100
Absolute numbers of neutrophils
Measured: at 1 month
Absolute numbers of neutrophils
Measured: at 2 months
Absolute numbers of neutrophils
Measured: at 3 months
Absolute numbers of neutrophils
Measured: at 6 months
Absolute numbers of neutrophils
Measured: at 12 months
Absolute numbers of neutrophils
Measured: through study completion, an average of 6 months
Absolute numbers of platelets
Measured: at 1 month
Absolute numbers of platelets
Measured: at 2 months
Absolute numbers of platelets
Measured: at 3 months
Absolute numbers of platelets
Measured: at 6 months
Absolute numbers of platelets
Measured: at 12 months
Absolute numbers of platelets
Measured: through study completion, an average of 6 months
Incidence of use of growth factors for poor hematopoietic reconstitution
Measured: up to one year
Acute graft-versus-host disease (GvHD) incidence
Measured: at 3 months
Chronic graft-versus-host disease (GvHD) incidence
Measured: at 24 months
Relapse incidence
Measured: at 12 months
Relapse incidence
Measured: at 24 months
Progression free survival
Measured: at 12 months
Progression free survival
Measured: at 24 months
Incidence of cytomegalovirus (CMV) infection
Measured: at 12 months
Incidence of Epstein-Barr virus (EBV) infection
Measured: at 12 months
Severe infections (CTAE grade 3-4)
Measured: at 3 months
Severe infections (CTAE grade 3-4)
Measured: at 6 months
Severe infections (CTAE grade 3-4)
Measured: at 12 months
Severe infections (CTAE grade 3-4)
Measured: at 24 months
Non-relapse mortality
Measured: at 24 months
Incidence of cardiac toxicities
Measured: at 12 months
Overall survival
Measured: at 12 months
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.
Measured: at 3 months
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.
Measured: at 3 months
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.
Measured: at 6 months
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.
Measured: at 6 months
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.
Measured: at 12 months
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.
Measured: at 12 months
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.
Measured: at 24 months
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.
Measured: at 24 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 1 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 3 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 6 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 12 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 24 months
Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
Measured: at 3 months
Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
Measured: at 6 months
Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
Measured: at 12 months
Immune reconstitution by analyzing T, B, NK, regulatory T cell levels in the peripheral blood
Measured: at 24 months
Ferritin levels
Measured: at 3 months
Ferritin levels
Measured: at 6 months
Ferritin levels
Measured: at 12 months
Ferritin levels
Measured: at 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2021
- Study start6 Jan 2022
- Primary completion6 Jan 2027 (estimated)
- Study completion6 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Idiopathic Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05126849
- Sponsor's protocol ID
- APHP200004
- Acronym
- HAPLO-EMPTY
- Status last verified
- Nov 2023
- First submitted
- 15 Oct 2021
- Last updated
- 24 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation With Post-transplant Cyclophosphamide in Patients With Acquired Refractory Aplastic Anemia or in Relapse After Immunosuppression: a Nationwide Phase II Study
- ClinicalTrials.gov ID
- NCT05126849
- Acronym / sponsor ID
- HAPLO-EMPTY / APHP200004
- Conditions
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 6 Jan 2022 (actual)
- Primary completion
- 6 Jan 2027 (estimated)
- Study completion
- 6 Jan 2027 (estimated)
- First posted
- 19 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Haploidentical allogeneic hematopoietic stem cell transplantation. | Experimental | Other: Allogenic transplantation1. 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. |
Who may qualify
- Ages
- 3 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- 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)
Key exclusion criteria (14 listed)
- With morphologic evidence of clonal evolution (patients with isolated bone marrow cytogenetic abnormalities are also eligible excepted chromosome 7 abnormalities and complex karyotype)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogenic transplantation1. 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. | Other | Haploidentical allogeneic hematopoietic stem cell transplantation. |
Primary outcome
Overall survival rate
Time frame: at 2 years
52 secondary outcomes
Graft failure incidence
Time frame: at 2 years
Neutrophils engraftment
Time frame: at day 100
Platelets engraftment
Time frame: at day 100
Absolute numbers of neutrophils
Time frame: at 1 month
Absolute numbers of neutrophils
Time frame: at 2 months
Absolute numbers of neutrophils
Time frame: at 3 months
Absolute numbers of neutrophils
Time frame: at 6 months
Absolute numbers of neutrophils
Time frame: at 12 months
Absolute numbers of neutrophils
Time frame: through study completion, an average of 6 months
Absolute numbers of platelets
Time frame: at 1 month
Absolute numbers of platelets
Time frame: at 2 months
Absolute numbers of platelets
Time frame: at 3 months
Absolute numbers of platelets
Time frame: at 6 months
Absolute numbers of platelets
Time frame: at 12 months
Absolute numbers of platelets
Time frame: through study completion, an average of 6 months
Incidence of use of growth factors for poor hematopoietic reconstitution
Time frame: up to one year
Acute graft-versus-host disease (GvHD) incidence
Time frame: at 3 months
Chronic graft-versus-host disease (GvHD) incidence
Time frame: at 24 months
Relapse incidence
Time frame: at 12 months
Relapse incidence
Time frame: at 24 months
Progression free survival
Time frame: at 12 months
Progression free survival
Time frame: at 24 months
Incidence of cytomegalovirus (CMV) infection
Time frame: at 12 months
Incidence of Epstein-Barr virus (EBV) infection
Time frame: at 12 months
Severe infections (CTAE grade 3-4)
Time frame: at 3 months
Severe infections (CTAE grade 3-4)
Time frame: at 6 months
Severe infections (CTAE grade 3-4)
Time frame: at 12 months
Severe infections (CTAE grade 3-4)
Time frame: at 24 months
Non-relapse mortality
Time frame: at 24 months
Incidence of cardiac toxicities
Time frame: at 12 months
Overall survival
Time frame: at 12 months
Quality of life questionnaire for adults
Time frame: at 3 months
Quality of life questionnaire for minors
Time frame: at 3 months
Quality of life questionnaire for adults
Time frame: at 6 months
Quality of life questionnaire for minors
Time frame: at 6 months
Quality of life questionnaire for adults
Time frame: at 12 months
Quality of life questionnaire for minors
Time frame: at 12 months
Quality of life questionnaire for adults
Time frame: at 24 months
Quality of life questionnaire for minors
Time frame: at 24 months
Proportion of patients with a donor chimerism of 90% or more
Time frame: at 1 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
35 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogenic transplantation in people with Refractory Idiopathic Aplastic Anemia and Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation, run by Assistance Publique - Hôpitaux de Paris at 35 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 35 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Regis Peffault de Latour, Pr (+33142385073, regis.peffaultdelatour@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival rate (time frame: at 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2023.