MUNC-CD34 for Familial Hemophagocytic Lymphohistiocytosis (FHL)

Inclusion criteria

• {"criterion_text":"- 1.\tPatient aged from 3 months up to 17 years old"}
• {"criterion_text":"- 2.\tPatient with a FHL caused by mutation of the UNC13D gene."}
• {"criterion_text":"- 3.\tComplete remission is defined by the normalization of clinical and laboratory parameters:"}
• {"criterion_text":"- 4.\tPatient eligible for an allogeneic HSCT in absence of an HLA geno-identical donor (at diagnostic or after failure of a previous HSCT (rejection or loss of the graft))"}
• {"criterion_text":"- 5.\tParental, guardian’s patient signed informed consent."}
• {"criterion_text":"- 6.\tFor patients of childbearing age : willing to use an effective method of contraception during the trial and for at least 12 months post-infusion"}
• {"criterion_text":"- 7.\tAffiliation to Social Security"}

Exclusion criteria

• {"criterion_text":"- 1)\tActive CNS encephalitis related to HLH"}
• {"criterion_text":"- 2)\tExistence of a matched –sibling donor"}
• {"criterion_text":"- 3)\tUnwillingness to return for follow-up during the 2 years study and lifelong for off study review."}
• {"criterion_text":"- 4)\tHIV-1 or 2 or HTLV1 infections."}
• {"criterion_text":"- 5)\tPatient on AME (state medical aid) (unless exemption from affiliation)"}
• {"criterion_text":"- 6)\tPregnancy or breast feeding in a post-partum female"}
• {"criterion_text":"- 7)\tDiagnosis of significant psychiatric disorder of the subject that could seriously impeded the ability to participate in the study"}
• {"criterion_text":"- 8)\tKnown allergies, hypersensitivity, or intolerance to any of busulfan, fludarabine, rituximab, G-CSF, plerixafor or excipients, or similar compounds"}
• {"criterion_text":"- 9)\tParticipation in another clinical study with an investigational drug within 30 days of inclusion."}

Primary endpoints

• {"endpoint_text":"- 1.\tIncidence of Transplantation Related Mortality (TRM) up to M3 post treatment.","definition_or_measurement_approach":"Incidence of Transplantation Related Mortality assessed through occurrence of death related to transplantation up to month 3 post treatment."}
• {"endpoint_text":"- 2.\tFrequency and severity of clinical AEs and laboratory parameters throughout the whole period of the research. Adverse event will be measured using CTCAE.","definition_or_measurement_approach":"Adverse events measured using CTCAE; frequency and severity of clinical AEs and laboratory parameters recorded throughout study."}
• {"endpoint_text":"- 3.\tIncidence of clinically detectable malignancy and/or abnormal clonal dominance assessed as related to study treatment M12 (Bone marrow analysis and VISA) Detection of Replication –Competent Lentivirus (RCL) at M12.","definition_or_measurement_approach":"Assessment at month 12 including bone marrow analysis and VISA for clonal dominance; detection of Replication-Competent Lentivirus (RCL) at M12."}

Secondary endpoints

• {"endpoint_text":"- 1.\tCharacterized the engraftment of DPs through hematopoietic reconstitution after IV infusion of MUNC-CD34: a.\tNeutrophil and platelet recovery (ANC> 500/µl, Platelets > 20.000/µl on two consecutive days without transfusion)","definition_or_measurement_approach":"Neutrophil recovery defined as ANC > 500/µl; platelet recovery defined as Platelets > 20,000/µl on two consecutive days without transfusion."}
• {"endpoint_text":"- 2.\tAssess the initial efficacy of treatment : a.\tThe Persistent HLH remission evaluated by the Disease-free survival (DFS) at M6. b.\tVCN in PBMC > 0.2 at M6.","definition_or_measurement_approach":"Efficacy assessed by Disease-free survival at month 6 and vector copy number (VCN) in PBMC > 0.2 at M6."}
• {"endpoint_text":"- 3.\tAssess the long-term safety and efficacy. a.\tThe Persistant HLH remission evaluated by the Disease-free survival (DFS) at M24 b.\tVCN in PBMC > 0.2 at M24. c.\tCorrection of degranulation function in T-CD3 at M24.","definition_or_measurement_approach":"Long-term efficacy/safety: DFS at month 24; VCN in PBMC > 0.2 at M24; correction of T‑cell degranulation function (T‑CD3) at M24."}
• {"endpoint_text":"- 4.\tEstimate of the cost of the complete procedure, from mobilisation to transplant and estimate of the 24 months total cost.","definition_or_measurement_approach":"Economic assessment estimating total cost from mobilisation to transplant and total 24‑month cost."}

France

Earliest CTIS Part Ii Submission Date

09-08-2024

Latest Decision Or Authorization Date

08-04-2026

Processing Time Days

607

Number Of Sites

7

Number Of Participants

5

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France