Safety Study of Gene Modified Donor T-cells Following TCR Alpha Beta Depleted Stem Cell Transplant

This is a Phase 1/2 study evaluating the safety and feasibility of BPX-501 T cells infused
after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell
transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine
whether BPX-501 infusion can enhance immune reconstitution and retain the graft versus
leukemia (GVL) effect, with the potential for reducing the severity and duration of severe
acute GvHD. The trial will evaluate the treatment of GvHD by the infusion of dimerizer drug
(AP1903/rimiducid) in those subjects who present with Grade III-IV acute GVHD, as well as
those subjects with Grade II gut/liver GvHD or with Grade I/II GvHD (skin only) who progress
or do not respond within 7 days to standard of care treatment.

Inclusion Criteria:

- Children with life-threatening hematological malignancies, deemed eligible for
allogeneic stem cell transplantation

- Children with non-malignant disorders amenable to be cured by an allograft

- Lack of HLA identical donor

- Life expectancy > 10 weeks

- Lansky/Karnofsky score > 50

Exclusion Criteria:

- Grade >II acute GvHD or chronic extensive GvHD at the time of inclusion

- Patient receiving an immunosuppressive treatment for GvHD treatment at the time of
inclusion

- Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal
value), or of renal function (creatinine clearance < 30 ml / min)

- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive
heart failure or left ventricular ejection fraction <40%)

- Current active infectious disease (including positive HIV serology or viral RNA)

- Serious concurrent uncontrolled medical disorder

- Pregnant or breast feeding female patient