Observational Follow-up Study of Haplo-identical Transplants in Fanconi Disease (HAPLO-FANCONI)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Fanconi Syndrome
• Intervention / Treatment: Other: Blood sampling

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

• Study Type: Observational
• Enrollment (Estimated): 18

Contacts and Locations

• Study Contact: Name: Matthieu RESCHE-RIGON, Pr; Phone Number: +33 1 42 49 97 42; Email: matthieu.resche-rigon@u-paris.fr
• Study Contact Backup: Name: Flore Sicre de Fontbrune, Dr; Phone Number: +33 1 42 49 42 67; Email: flore.sicre-de-fontbrune@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Patient with Fanconi disease

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patient with Fanconi disease	Other: Blood sampling; Additional blood samples at J100, M6, M12, M24

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival Rate	2 years after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Absolute neutrophils count		At 1 month
Absolute neutrophils count		At 3 months
Absolute neutrophils count		At 6 months
Absolute neutrophils count		At 12 months
Absolute neutrophils count		At 24 months
Absolute number of platelets		At 1 month
Absolute number of platelets		At 3 months
Absolute number of platelets		At 6 months
Absolute number of platelets		At 12 months
Absolute number of platelets		At 24 months
Incidence of grade 2 to 4 Acute Graft versus Host Disease		At 3 months
Incidence of Acute cortico-resistant Graft versus Host Disease		At 3 months
Incidence of Chronic Graft versus Host Disease		At 24 months
Incidence of relapse		At 12 months
Incidence of relapse		At 24 months
Progression free survival		At 12 months
Progression free survival		At 24 months
Incidence of reactivation of cytomegalovirus infection		At 12 months
Incidence of reactivation of Epstein Barr virus infection		At 12 months
Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 3 months
Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 6 months
Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 12 months
Incidence of severe infection of grade 4 and above according to Common Terminology Criteria for Adverse Events (CTCAE)		At 24 months
Graft-versus-host disease-free, relapse-free survival (GRFS)		At 24 months
Incidence of cardiac toxities		At 12 months
Overall survival		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.	At inclusion
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
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
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
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
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
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
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
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
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
Rate of chimerism		At 1 month
Rate of chimerism		At 3 months
Rate of chimerism		At 6 months
Rate of chimerism		At 12 months
Rate of chimerism		At 24 months
Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		3 months after transplant
Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		6 months after transplant
Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		12 months after transplant
Immune reconstitution by analyzing T, B, natural killer (NK), regulatory T cell levels in the peripheral blood		24 months after transplant
Ferritine levels		At 3 months
Ferritine levels		At 6 months
Ferritine levels		At 12 months
Ferritine levels		At 24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Fanconi Syndrome; Fanconi Anemia
• Other Study ID Numbers: APHP221272

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No