Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant

This is a Phase1/2 dose escalation study evaluating the safety and feasibility of BPX-501
infused after partially mismatched, related (haploidentical), T cell-depleted HSCT. The
purpose of this clinical trial is to determine whether BPX-501 infusion can facilitate
engraftment, enhance immune reconstitution and potentially improve the graft versus leukemia
(GVL) effect, with the potential for reducing the severity and duration of severe acute graft
versus host disease (GvHD). The trial will evaluate the treatment of GvHD by the infusion of
dimerizer drug (AP1903) in those subjects who present with severe GvHD (Grades III and IV) as
well as those subjects with Grade I and II who progress or do not respond to corticosteroid
therapy within 4 days.

Inclusion Criteria:

1. Signed informed consent

2. Age ≥ 18 years and ≤ 65 years

3. Deemed eligible for allogeneic stem cell transplantation

4. Lack of suitable conventional donor (i.e. 8/8 related or unrelated donor) or presence
of rapidly progressive disease not permitting time to identify an unrelated donor

5. HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw,
and DRBl, and loci

- A minimum genotypic identical match of 4/8 is required.

- 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, and HLA-DRB1

6. Subjects with adequate organ functions as measured by:

1. Cardiac: Left ventricular ejection fraction at rest must be ≥ 45%

2. Hepatic: Bilirubin ≤ 2.5 mg/dL and ALT, AST and Alkaline Phosphatase < 5 x ULN

3. Renal: Serum creatinine within normal range for age or creatinine clearance, or
with a recommended GFR ≥ 50 mL/min/1.73m2

4. Pulmonary: FEV 1, FVC and DLCO (diffusion capacity) ≥ 50% predicted (corrected
for hemoglobin); or O2 saturation > 92% on room air

7. Clinical diagnosis of one of the following:

a. Acute Leukemia (includes T lymphoblastic lymphoma) in 2nd or subsequent complete
remission (CR) i. Acute Lymphoblastic Leukemia (ALL) in 2nd or subsequent CR. ALL
shall be morphologic remission at the time of transplant. Morphologic remission is
defined that subjects with normal neutrophil and platelet counts, less than 5% blast
cells in a bone marrow (BM) smear and no extramedullary disease ii. Acute Myeloid
Leukemia (AML) in 2nd or subsequent CR with or without persistent minimal residual
disease b. High-risk ALL in 1st CR (including features such as those in i-iii) i.
Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), MLL rearrangements ii.
Subjects over 30 years of age, or iii. Time to complete remission was greater than 4
weeks. c. High-risk AML in 1st CR (including features such as those listed in i-vii)
i. Greater than 1 cycle of induction therapy required to achieve remission ii.
Preceding myelodysplastic syndrome (MDS) iii. Presence of FLT3 abnormalities iv. FAB
M6 or M7 leukemia v. Adverse cytogenetics for overall survival such as those
associated with MDS vi. Complex karyotype (>3 abnormalities), or vii. Any of the
following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with other abnormalities
except for t(8;21), t(9;11), inv(16) or t(16;16)], t(l1;19)(q23;p13.1) d. High risk
Myelodysplastic Syndrome e. Non-Hodgkin's Lymphoma relapsed after autologous
transplantation f. Non-Hodgkin's Lymphoma with insufficient autologous hematopoietic
stem cells to undergo autologous transplantation g. CML i. in first chronic phase that
has not attained at least a complete cytogenetic remission after exposure to at least
3 tyrosine kinase inhibitors ii. in accelerated phase that has not attained at least a
complete cytogenetic remission iii. in second chronic phase

8. Performance status: Karnofsky score ≥60%.

9. Patient with hematologic malignancy not responding to /or not eligible for
conventional therapy and are approved by Sponsor

Exclusion Criteria:

1. HLA 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) related or unrelated donor able to donate.

2. Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.

3. Pregnancy or breast-feeding.

4. Evidence of HIV infection or known HIV positive serology.

5. Current uncontrolled bacterial, viral or fungal infection (currently taking medication
with evidence of progression of clinical symptoms or radiologic findings). The
treating physician will make final determination.

6. Non-hematologic malignancy within prior three (3) years, with the exception of
squamous cell or basal cell skin carcinoma.

7. Prior allogeneic hematopoietic stem cell transplant.

8. Subjects with a history of primary idiopathic myelofibrosis.

9. Bovine product allergy.