Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
This study will evaluate pediatric patients with malignant or non-malignant blood cell
 disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa
 and beta cells that comes from a partially matched family donor. The study will assess
 whether immune cells, called T cells, from the family donor, that are specially grown in the
 laboratory and given back to the patient along with the stem cell transplant can help the
 immune system recover faster after transplant. As a safety measure these T cells have been
 programmed with a self-destruct switch so that they can be destroyed if they start to react
 against tissues (graft versus host disease).
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 in those patients with hematologic
 disorders, with the potential for reducing the severity and duration severe acute graft
 versus host disease (GvHD).

 The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug
 (AP1903/rimiducid) in those subjects who present with GVHD that does not adequately respond
 to standard of care therapy.
Inclusion Criteria:

 1. Age > 1 month and < 26 years

 2. Life expectancy > 10 weeks

 3. Subjects deemed eligible for allogeneic stem cell transplantation.

 4. Subjects with life-threatening hematological malignancies (high-risk ALL in 1st CR,
 ALL in 2nd or subsequent CR, AML in 1st CR, AML in 2nd or subsequent CR,
 myelodysplastic syndromes, non-Hodgkin lymphomas in 2nd or subsequent CR, other
 hematologic malignancies eligible for stem cell transplantation per institutional
 standard);

 5. Non-malignant disorders amenable to cure by an allograft:

 1. primary immune deficiencies,

 2. severe aplastic anemia not responding to immune suppressive therapy,

 3. osteopetrosis,

 4. hemoglobinopathies, (thalassemias, and sickle cell anemia, and Diamond-Blackfan
 anemia among others)

 5. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal
 malignant evolution (MDS, AML) Note: Subjects will be eligible if they meet
 either item 4 OR item 5.

 6. Lack of suitable conventional donor (HLA identical sibling or HLA phenotypically
 identical relative or 10/10 unrelated donor evaluated using high resolution molecular
 typing) or presence of rapidly progressive disease not permitting time to identify an
 unrelated donor

 7. A minimum genotypic identical match of 5/ 10 is required.

 8. The donor and recipient must be identical, as determined by high resolution typing, at
 least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-
 DRB1 and HLA-DQB1.

 9. Lansky/Karnofsky score > 50

 10. Signed written informed consent

 Exclusion Criteria:

 1. Greater than Grade II acute GVHD or chronic extensive GVHD due to a previous allograft
 at the time of inclusion

 2. Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous
 allograft at the time of inclusion

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

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

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

 6. Serious concurrent uncontrolled medical disorder

 7. Pregnant or breastfeeding subject

 8. For subjects who have received more than 1 x 10E5 alpha/beta T cells/kg with the graft
 infusion the clinical trial site must contact the sponsor for approval to be eligible
 to receive BPX-501 infusion.