Clinical trial NCT05903365: Observational Follow-up Study of Haplo-identical Transplants in Fanconi Disease
Official title: Etude Observationnelle de Suivi Des Greffes Haplo-identique Dans la Maladie de Fanconi
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Fanconi Syndrome
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-06-15
Enrollment: 18
Sex: ALL
Minimum age (years): 6
Maximum age (years): 60
Standard ages: CHILD
ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patient with Fanconi disease

Brief summary: This observational protocol will allow for an independent, prospective evaluation of the improvement in survival of patients with Fanconi disease in hematological deadlock due to the absence of an HLA-identical donor and having received a haploidentical transplant.

Detailed description: Fanconi's disease is characterised by a constitutional defect in DNA repair which results in the occurrence of bone marrow failure and haematological malignancies, mainly myeloid: at the age of 40, the cumulative incidence of these two types of pathology reaches almost 100%. The only curative treatment for haemtalogocial diseases is allogenic hematopoietic stem cell transplant. Transplantation modalities must be adapted to the particular susceptibility of these patients to DNA bridging agents and radiotherapy. HSC transplantation is indicated with an unaffected matched related or matched unrelated donor when the patient has severe bone marrow failure or a poor prognostic clonal evolution (cytogenetic evolution or proven haemopathy). Alternative transplants (9/10 pheno-identical, haplo-identical and placental blood donors) were no longer proposed in most cases due to the frequency of severe complications (graft-versus-host disease, viral infections) and the catastrophic medium-term survival of around 40% (Dufort, Bone Marrow Transplant 2012, Gluckman Biol Blood Marrow Transplant. 2007). The development over the last decade of new haploidentical or phenoidentical 9/10 transplant protocols with unmodified grafts and GVH prophylaxis with post-transplant cyclosphosphamide or ex vivo T-depletion adapted to the particular susceptibility of patients with Fanconi disease has reduced the incidence of these severe complications.

This observational protocol will allow for an independent, prospective evaluation of the improvement in survival of patients with Fanconi disease in hematological deadlock due to the absence of an HLA-identical donor and having received a haploidentical transplant

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Fanconi disease confirmed by chromosome breakage test and/or genetic analysis
* aged between 6 months and 60 years
* with severe pancytopenia (2 of the following criteria: reticulocytes \< 60 G/L, PNN \< 0.5 G/L and/or platelets \< 20 G/L or patients with more than 6 transfusions in the last 12 months)
* with clonal progression (poor prognostic cytogenetics, myelodysplastic syndrome or acute leukaemia)
* with an unaffected haploidentical donor
* having signed the consent after having read the information note, consent of both parents for minors, of the guardian for patients under guardianship
* having a social security scheme (beneficiary or entitled person)

Exclusion Criteria:

* with an unaffected matched related or HLA 10/10 matched unrelated donnor
* under guardianship

Primary outcomes:
measure: Overall Survival Rate
timeFrame: 2 years after transplant
Secondary outcomes:
measure: Engraftment
timeFrame: At day 100
measure: Absolute neutrophils count
timeFrame: At 1 month
measure: Absolute neutrophils count
timeFrame: At 3 months
measure: Absolute neutrophils count
timeFrame: At 6 months
measure: Absolute neutrophils count
timeFrame: At 12 months
measure: Absolute neutrophils count
timeFrame: At 24 months
measure: Absolute number of platelets
timeFrame: At 1 month
measure: Absolute number of platelets
timeFrame: At 3 months
measure: Absolute number of platelets
timeFrame: At 6 months
measure: Absolute number of platelets
timeFrame: At 12 months
measure: Absolute number of platelets
timeFrame: At 24 months
measure: Incidence of grade 2 to 4 Acute Graft versus Host Disease
timeFrame: At 3 months
measure: Incidence of Acute cortico-resistant Graft versus Host Disease
timeFrame: At 3 months
measure: Incidence of Chronic Graft versus Host Disease
timeFrame: At 24 months
measure: Incidence of relapse
timeFrame: At 12 months
measure: Incidence of relapse
timeFrame: At 24 months
measure: Progression free survival
timeFrame: At 12 months
measure: Progression free survival
timeFrame: At 24 months
measure: Incidence of reactivation of cytomegalovirus infection
timeFrame: At 12 months
measure: Incidence of reactivation of Epstein Barr virus infection
timeFrame: At 12 months
measure: Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: At 3 months
measure: Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: At 6 months
measure: Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: At 12 months
measure: Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)
timeFrame: At 24 months
measure: Graft-versus-host disease-free, relapse-free survival (GRFS)
timeFrame: At 24 months
measure: Incidence of cardiac toxities
timeFrame: At 12 months
measure: Overall survival
timeFrame: At 12 months
measure: Quality of Life questionnaire for adults
timeFrame: At inclusion
measure: Quality of Life questionnaire for adults
timeFrame: At 3 months
measure: Quality of Life questionnaire for adults
timeFrame: At 6 months
measure: Quality of Life questionnaire for adults
timeFrame: At 12 months
measure: Quality of Life questionnaire for adults
timeFrame: At 24 months
measure: Quality of life questionnaire for minors
timeFrame: At inclusion
measure: Quality of life questionnaire for minors
timeFrame: At 3 months
measure: Quality of life questionnaire for minors
timeFrame: At 6 months
measure: Quality of life questionnaire for minors
timeFrame: At 12 months
measure: Quality of life questionnaire for minors
timeFrame: At 24 months
measure: Rate of chimerism
timeFrame: At 1 month
measure: Rate of chimerism
timeFrame: At 3 months
measure: Rate of chimerism
timeFrame: At 6 months
measure: Rate of chimerism
timeFrame: At 12 months
measure: Rate of chimerism
timeFrame: At 24 months
measure: Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
timeFrame: 3 months after transplant
measure: Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
timeFrame: 6 months after transplant
measure: Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
timeFrame: 12 months after transplant
measure: Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood
timeFrame: 24 months after transplant
measure: Ferritine levels
timeFrame: At 3 months
measure: Ferritine levels
timeFrame: At 6 months
measure: Ferritine levels
timeFrame: At 12 months
measure: Ferritine levels
timeFrame: At 24 months
Other outcomes:
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