Observational Follow-up Study of Haplo-identical Transplants in Fanconi Disease

Fanconi Syndrome Clinical Trial

— HAPLO-FANCONI  

Official title:

Etude Observationnelle de Suivi Des Greffes Haplo-identique Dans la Maladie de Fanconi

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05903365
• Other study ID #: APHP221272
• Status: Not yet recruiting
• Start date: June 2023
• Est. completion date: March 2028

Study information

• Verified date: April 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Flore Sicre de Fontbrune, Dr
• Phone: +33 1 42 49 42 67
• Email: flore.sicre-de-fontbrune[@]aphp.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: March 2028
• Est. primary completion date: March 2028
• Gender: All
• Age group: 6 Months to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Fanconi Anemia
• Fanconi Syndrome

Intervention

Other:
• Blood sampling
Additional blood samples at J100, M6, M12, M24

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival Rate		2 years after transplant
Secondary	Engraftment	Engraftment at least 3 consecutive days with neutrophils > 0.5 G/L and 7 consecutive days with platelets > 20 G/L, with predominantly whole blood donor chimerism	At day 100
Secondary	Absolute neutrophils count		At 1 month
Secondary	Absolute neutrophils count		At 3 months
Secondary	Absolute neutrophils count		At 6 months
Secondary	Absolute neutrophils count		At 12 months
Secondary	Absolute neutrophils count		At 24 months
Secondary	Absolute number of platelets		At 1 month
Secondary	Absolute number of platelets		At 3 months
Secondary	Absolute number of platelets		At 6 months
Secondary	Absolute number of platelets		At 12 months
Secondary	Absolute number of platelets		At 24 months
Secondary	Incidence of grade 2 to 4 Acute Graft versus Host Disease		At 3 months
Secondary	Incidence of Acute cortico-resistant Graft versus Host Disease		At 3 months
Secondary	Incidence of Chronic Graft versus Host Disease		At 24 months
Secondary	Incidence of relapse		At 12 months
Secondary	Incidence of relapse		At 24 months
Secondary	Progression free survival		At 12 months
Secondary	Progression free survival		At 24 months
Secondary	Incidence of reactivation of cytomegalovirus infection		At 12 months
Secondary	Incidence of reactivation of Epstein Barr virus infection		At 12 months
Secondary	Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 3 months
Secondary	Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 6 months
Secondary	Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 12 months
Secondary	Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 24 months
Secondary	Graft-versus-host disease-free, relapse-free survival (GRFS)		At 24 months
Secondary	Incidence of cardiac toxities		At 12 months
Secondary	Overall survival		At 12 months
Secondary	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.	At inclusion
Secondary	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.	At 3 months
Secondary	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.	At 6 months
Secondary	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.	At 12 months
Secondary	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.	At 24 months
Secondary	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.	At inclusion
Secondary	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.	At 3 months
Secondary	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.	At 6 months
Secondary	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.	At 12 months
Secondary	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.	At 24 months
Secondary	Rate of chimerism		At 1 month
Secondary	Rate of chimerism		At 3 months
Secondary	Rate of chimerism		At 6 months
Secondary	Rate of chimerism		At 12 months
Secondary	Rate of chimerism		At 24 months
Secondary	Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		3 months after transplant
Secondary	Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		6 months after transplant
Secondary	Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		12 months after transplant
Secondary	Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		24 months after transplant
Secondary	Ferritine levels		At 3 months
Secondary	Ferritine levels		At 6 months
Secondary	Ferritine levels		At 12 months
Secondary	Ferritine levels		At 24 months