The objective of this clinical trial is to develop a cell therapy for Fanconi Anemia which enables enhanced donor hematopoietic and immune reconstitution with decreased toxicity by transplanting depleted stem cells from a donor with and without using an experimental antibody treatment called JSP-191 as a part of conditioning. This experimental treatment will hopefully cause fewer side effects than chemotherapy (the current standard of care method).
Participants will be administered the conditioning regimen, are assessed until they receive the depleted stem cell infusion, and will be followed for up to 2 years after the cell infusion.
Fanconi Anemia diagnosis as demonstrated by abnormal chromosome breakage studies with increased sensitivity to mitomycin-C (MMC) or diepoxybutane (DEB) and at least one mutation in a known Fanconi-associated gene
Bone marrow failure (defined by reduction in at least one cell line on two separate occasions at least one month apart (e.g., platelet count of <100,000 per cubic millimeter, hemoglobin <9 gm/dl and/or absolute neutrophil count (ANC) of <1000/mm)
Age of ≥2 years
Consenting ≥5/10 HLA-matched related or unrelated donor available for apheresis
Patients with available and consenting 10/10 HLA-identical sibling donor for apheresis
Patients with any acute or uncontrolled infections at the time of enrollment, including bacterial, fungal or viral
Patients who are seropositive for HIV-I/II or HTLV-I/II.
Patients receiving any other investigational agents or other biological, chemotherapy, or radiation therapy within 14 days of enrollment
Sequential
JSP191
DrugParticipants will receive a single IV dose at start of conditioning
CliniMACS Prodigy System
DeviceThe device used to remove the αβ+T cells from donor stem cell transplant before being given to the recipient
Depleted Stem Cell Transplant
Biological/VaccineTCRαβ+ T-cell/CD19+ B-cell depleted hematopoietic cells will be administered by IV after completion of conditioning regimen.
Rabbit Anti-Thymoglobulin (rATG)
Biological/Vaccine3 consecutive daily doses of rATG will be given by IV during conditioning
Cyclophosphamide
Drug4 consecutive daily doses of cyclophosphamid will be given by IV during conditioning
Fludarabine
Drug4 consecutive daily doses of fludarabine will be given by IV during conditioning
Rituximab
Drug1 dose of rituximab will be given at the end of conditioning
Number of participants without grade 3 and 4 treatment-emergent adverse events (TEAEs) (infusion related reactions).
Recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Number of participants without grade 3 and 4 treatment-emergent adverse events (TEAEs) (infusion related reactions) following infusion of TCRαβ+ T-cell/CD19+ B-cell depleted hematopoietic graft transplantation
Number of participants able to achieve donor engraftment
Participants have achieved engraftment when absolute Neutrophil Count (ANC) is above 500/mm\^3 for three consecutive laboratory values obtained on different days post cell transplantation with \>1% CD15 donor chimerism
Number of participants who are able to have donor engraftment persist at the same rate or better compared to alternative hematopoietic cell transplant regimens for this patient population
Serum concentration of JSP191
Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion
Serum concentration of rATG
Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion
Serum concentration of fludarabine
Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion
Participants who do not develop mucositis
Mucositis incidence will be scored using the CTC criteria
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Porteus, Matthew, MD
Lead sponsor
Stanford University
Sponsor institution
