Lentivirally Redirected CD123 Autologous T Cells in AML

This is a phase 1 study to determine the safety, feasibility, and efficacy of CART123 cells
following lymphodepleting chemotherapy in patients with relapsed/refractory AML. Subjects
will be treated with IV administration of CART123 cells using a split dosing approach (10%
Day 0, 30% Day 1; 60% Day 2).

The total dose administered to each subject will be based on body weight obtained at the time
of apheresis. Thus, the target total transduced dose is 1-2x106/kg CART-123 cells, preceded
by lymphodepleting chemotherapy. The protocol-specified minimum acceptable dose for infusion
is 1x105 CART cells/kg.

It is recommended per routine clinical care, that all subjects with marrow aplasia at Day
28+/-5 undergo allogeneic hematopoietic cell transplantation (alloHCT) as a rescue strategy.
If required, this procedure will be performed as part of routine care, outside of the scope
of this research study, however subjects will continue to be followed on study. All subjects
should therefore have a previously identified stem cell donor in order to participate in this
study. Please see Section 6.8 for additional details.

All subjects will be followed monthly for up to 6 months post the first CART123 cell infusion
(Day 0). Thereafter subjects will be transitioned into LTFU for up to 15 years post infusion.

Inclusion Criteria:

1. Male or female subjects 18 years of age or older

2. Subjects with active acute myeloid leukemia (AML) with no available curative treatment
options using currently available therapies. Specifically:

1. AML that has not achieved a complete remission or morphologic leukemia free state
by ELN criteria (Döhner et al., 2017 Blood, 129(4):424-447); partial remission or
refractory disease (including primary refractory) are eligible. Or:

2. AML relapsed following allogeneic stem cell transplantation (including MDS
evolved to AML post-allogeneic stem cell transplantation). Note: morphologic
relapse is not required; persistent/recurrent disease-associated molecular,
phenotypic or cytogenetic abnormalities (measurable residual disease, MRD) at any
time after allogeneic HCT is eligible

3. Subjects with relapsed disease after prior transplant must meet one of the following:

a. Subjects with relapsed disease after prior allogeneic HCT (myeloablative or
non-myeloablative) will be eligible if they meet all other inclusion criteria and i.
Have no residual donor cells (by STR analysis on 2 occasions separated by at least 1
month), OR: ii. Donor cells are present but there is no active GVHD (>Gr II), subject
does not require systemic immunosuppression and is more than 3 months from transplant,
and at least 1 month off GVHD prophylaxis.

b. Subjects with relapsed disease after prior autologous or syngeneic HCT will be
eligible if they meet all other inclusion criteria and it has been more than 3 months
from transplant.

4. Subjects must have a suitable stem cell donor available who may donate cells in the
event the subject needs to undergo an allogeneic HCT. Donor may be matched or
mismatched and must be found to be suitable according to the institution's standard
criteria; donors must be fully cleared to proceed as the donor.

5. Satisfactory organ functions:

1. Creatinine ≤ 1.6 mg/dl

2. ALT/AST must be ≤5 x upper limit of normal unless related to disease

3. Direct bilirubin or total bilirubin < 2.0mg/dl, unless subject has Gilbert's
syndrome (≤3.0 mg/dL);

4. Left ventricular ejection fraction > 40% as confirmed by ECHO/MUGA

6. ECOG Performance status 0-2.

7. Written informed consent is given.

8. No contraindications for leukapheresis.

9. Subjects of reproductive potential must agree to use acceptable birth control methods
(as described in protocol Section 4.3).

Exclusion Criteria:

1. Pregnant or lactating (nursing women) women.

2. Patients with relapsed AML with t(15:17).

3. HIV infection.

4. Active hepatitis B or hepatitis C infection.

5. Concurrent use of systemic steroids or immunosuppressant medications. Recent or
current use of inhaled steroids or physiologic replacement with hydrocortisone is not
exclusionary. For additional details regarding use of steroids while on study, please
see Section 5.5.

6. Any uncontrolled active medical disorder that would preclude participation as
outlined.

7. Subjects with signs or symptoms indicative of CNS involvement. A CNS evaluation should
be performed as clinically appropriate to rule out CNS involvement.

8. Known history of allergy or hypersensitivity to study product excipients (human serum
albumin, DMSO, and Dextran 40).

9. Class III/IV cardiovascular disability according to the New York Heart Association
Classification (see Appendix 2).

10. Patients with a known history or prior diagnosis of optic neuritis or other
immunologic or inflammatory disease affecting the central nervous system, and
unrelated to leukemia or previous leukemia treatment.

11. Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on
medical management, within 2 weeks of the Screening/Enrollment visit.