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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Participants will receive a single IV dose at start of conditioning
The device used to remove the αβ+T cells from donor stem cell transplant before being given to the recipient
TCRαβ+ T-cell/CD19+ B-cell depleted hematopoietic cells will be administered by IV after completion of conditioning regimen.
3 consecutive daily doses of rATG will be given by IV during conditioning
4 consecutive daily doses of cyclophosphamid will be given by IV during conditioning
4 consecutive daily doses of fludarabine will be given by IV during conditioning
1 dose of rituximab will be given at the end of conditioning
Stanford University
Stanford, California, United States
RECRUITINGNumber 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
Time frame: From start of conditioning regimen administration until cell infusion (up to 30 days)
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
Time frame: Up to 2 years post-cell infusion
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
Time frame: Assessed at Day +42 post-cell infusion
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
Time frame: Assessed at Day +100 post-cell infusion
Serum concentration of JSP191
Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion
Time frame: Prior to start of conditioning regimen, and 5 minutes, 4 hours, +2, +3, +4, +6, +8, +10 days after start of conditioning regimen, and day of cell infusion
Serum concentration of rATG
Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion
Time frame: Prior to start of rATG infusion; 15 minutes after first, second, and third rATG infusion; day of cell infusion; and week +1, week +2 and week +12 post cell infusion
Serum concentration of fludarabine
Assessed as serum concentrations in the peripheral blood from administration until time of cell infusion
Time frame: Prior to start of fludarabine infusion, and 15 minutes, 1 hour, 3 hours, and 6 hours after the fludarabine infusion
Participants who do not develop mucositis
Mucositis incidence will be scored using the CTC criteria
Time frame: Start of conditioning regimen until +12 weeks post-cell infusion (up to 15 weeks)
Participants who do not develop veno-occlusive disease (VOD)
VOD incidence will be scored using the Modified Seattle criteria
Time frame: Start of conditioning regimen until +12 weeks post-cell infusion (up to 15 weeks)
Number of participants who achieve hematopoietic recovery
Hematopoietic recovery defined by hemoglobin \>8g/dL and platelets \>20k/dL without transfusion support achieved on 7 days post-graft transplantation documented on hematologic monitoring
Time frame: Up to 107 weeks (after start of conditioning regimen through Week +104 post-cell infusion)
Number of participants who achieve donor engraftment
Engraftment measured as peripheral blood (total, CD15+, CD3+, CD19+, CD56+, and CD34+) and bone marrow (total and CD34+) chimerism by STR analysis
Time frame: Weeks +1 through +104 post-cell infusion
Number of participants who achieve immunologic recovery
Immunologic recovery defined as \>200/uL CD3+ T-cells and as assessed by percent and absolute numbers of T (CD3), B (CD19) and NK (CD56) cells by CBC differential studies and flow cytometry for lymphocyte lineages
Time frame: Weeks +1 through +104 post-cell infusion
Number of participants who develop Grade I-IV acute graft-vs-host disease (GvHD)
Time frame: Day +100 post-cell infusion
Number of participants who develop chronic graft-vs-host disease (GvHD)
Time frame: Day +100 through Week +104 post-cell infusion
Number of participants who achieve disease-free survival
Disease-free defined by improved DEB-induced chromosomal breakage analysis in peripheral blood lymphocyte cultures
Time frame: Up to 104 weeks (from time of cell infusion through Week +104)
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