Arm 1: Phase 1 Study of monovalent CD123-Specific Adapter (SPRX002) and Universal CAR-Modified T cell (ARC-T Cells) for the Treatment of Patients with Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

Protocol # :
Acute Myeloid Leukemia
Myelodysplastic Syndromes
Disease Sites
Other Hematopoietic
Myeloid and Monocytic Leukemia
Principal Investigator
Chen, Evan, Chris

Trial Description

The purpose of this study is to evaluate the safety and preliminary activity of ARC-T
cells and SPRX002 in participants with relapsed or refractory acute myeloid leukemia
(AML) or high-risk myelodysplastic syndrome (MDS)

Eligibility Requirements

Inclusion Criteria:

1. 18 years or older

2. For AML Subjects: WHO-confirmed AML, other than APL, with no standard treatment
options available (WHO AML Criteria 2016)

a. Relapsed or refractory disease after at least 1 line of therapy, as defined by
the following: i. Relapsed: Bone marrow blasts ≥5% following achievement of

ii. Refractory: Failure to achieve CR/Cri/MLFS with evidence of persistent leukemia by
blood and/or bone marrow examination after any of the following:

1. Failure on at least 1 cycle of an anthracycline-based induction therapy

2. At least 1 cycle of high or intermediate dose cytarabine containing induction

3. At least 2 cycles of VEN-based lower intensity therapy, e.g., with HMA, or LDAC or

4. At least 4 cycles of HMA-based therapy without venetoclax

3.For MDS Subjects: A diagnosis of MDS and ≥10% bone marrow blasts with indication of
high-risk disease defined as those having resistant or refractory disease to at least one
course of therapy including hypomethylating agents (e.g., decitabine or 5-azacitidine)
given at conventional dose, schedule, and duration (e.g., cycle every 28 days and for at
least 4 cycles) with or without venetoclax or other agents. Failure is defined as failure
to attain a response, or relapse after prior response to HMA therapy per the modified IWG

4. Patients relapsing after allogeneic hematopoietic stem cell transplant (HSCT) >3
months prior are eligible if they have recovered from all transplant-related
toxicities and are off all immunosuppression for at least 6 weeks.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

6. Adequate organ function, including renal and hepatic function based on last clinical
assessment performed within the screening period

1. Creatinine clearance ≥50 ml/min (Cockcroft-Gault or 24-hour urine collection in
cases in which Cockroft-Gault is unreliable or if preferred by physician) and not on

2. Alanine aminotransferase <3 x upper limit of normal (ULN)

3. Aspartate aminotransferase <3 x the upper limit of normal (ULN)

4. Total bilirubin <2 x upper limit of normal (ULN) (except for patients with known or
suspected history of Gilbert's Syndrome where up to 3x ULN is allowed)

5. Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiography (ECHO) or
multi-gated acquisition (MUGA) scan

6. Pulse oxygenation ≥92% on room air

7. Prothrombin time test (PTT), prothrombin time (PT)/international normalized ratio
(INR) <1.5 x ULN, unless on a stable dose of anti-coagulant for thromboembolic event
(patients with any history of thromboembolic stroke; or history or Grade 2 (G2) or
greater hemorrhage within 60 days are excluded)

7. Resolution of adverse events (AEs) from any prior systemic anticancer therapy,
radiotherapy, or surgery to Grade 1 or baseline (except G2 alopecia and G2
sensory neuropathy)

8. Prior allogeneic stem cell transplant is allowed, provided the subject has
recovered from all AEs, there is no ongoing graft-versus-host-disease (GvHD)
and subject is not on taking any immunosuppressive medications to prevent GvHD

9. Male and females of childbearing potential must agree to use highly effective
methods of birth control through 6 months after the dose of study treatment.

10. Patients must have an identified potential donor and transplant strategy/plan
prior to initiation of the lymphodepletion regimen to ensure availability of
hematopoeitic stem cells (HSCs) for potential urgent allogeneic HSC transplant
(HSCT) if needed for persistent bone marrow aplasia without evidence of
residual leukemia. Transplant decision making would be a discussion between
subject and investigator due to potential for treatment-related mortality and
is not required

11. Willing to comply with and able to tolerate study procedures, including
Long-Term Safety Follow-up lasting up to 15 years

12. Life expectancy > 3 months

13. Subject's apheresis product from non-mobilized cells is received and accepted
for cell processing by manufacturing site. NOTE: apheresis will be accepted
only after all other eligibility criteria have been met

Exclusion Criteria:

1. Patients with acute promyelocytic leukemia (APL) or EMD-only disease

2. Patients with active CNS involvement. Subjects may be cleared of CNS involvement if
there has been no evidence of CNS involvement for at least 3 months prior to
enrollment. For instance, CSF samples showing no evidence of blasts by CSF cytology,
no clinical signs or symptoms, or no radiological findings concerning for CNS

3. Hyperleukocytosis (≥25,000 blasts/μL) or rapidly progressive disease that in the
estimation of the investigator and sponsor would compromise ability to complete
study therapy. (Note: Subjects may be receiving or may receive hydroxyurea to
maintain or control hyperleukocytosis)

4. Previous treatment with an investigational gene or chimeric antigen receptor therapy
(Note: May be permitted after discussion with Medical Monitor)

5. Previous treatment with a CD123 directed therapy (T-cell engager or ADC)

6. Use of any anti-AML/MDS directed chemotherapy or targeted therapy (except
hydroxyurea therapy) or immunosuppressive agents (physiologic doses are allowed),
within 14 days or 5 half-lives (whichever is shorter) prior to the date of
leukapheresis and use of any anti-AML/MDS directed monoclonal antibody within 28
days prior to date of leukapheresis

7. Known infection with Human Immunodeficiency Virus or Human T-Cell leukemia/lymphoma
virus type 1 (HTLV-1)

8. A known hypersensitivity or severe allergy to study drug components including
dimethyl sulphoxide (DMSO) and human serum albumin

9. Contraindication to cyclophosphamide or fludarabine

10. Subject has systemic fungal, bacterial, viral or other infection that is exhibiting
ongoing signs/symptoms related to the infection without improvement despite
appropriate treatment (Note: Isolated fever may not constitute active infection in
and of itself, (e.g., related to disease)

11. Severe uncontrolled intercurrent illness including:

1. Cardiovascular disease

2. Symptomatic congestive heart failure

3. Unstable angina, arrythmia, or myocardial infarction (MI) within 6 months prior
to screening

4. Significant pulmonary dysfunction

5. Uncontrolled thromboembolic events or recent severe hemorrhage

6. Any history of pulmonary embolism (PE) ever or deep vein thrombosis (DVT)
within 3 months of screening. Therapeutic dosing of anticoagulants (e.g.,
warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for
history of DVT if greater than 3 months from time of screening) Note: Central
line thrombosis not requiring anticoagulation will not be excluded and will not
require a 3-month screening window

7. Autoimmune disease

12. Seropositive for and with evidence of active hepatitis B or C infection at time of

1. Subjects with a history of hepatitis B but have received antiviral therapy and
have non-detectable viral DNA for 6 months are eligible

2. Subjects seropositive because of hepatitis B virus vaccine with no signs or
active infection are eligible

3. Subjects who had hepatitis C but have received antiviral therapy and show no
detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible

13. Any sign of active CNS pathology within 6 months of screening including history of
epilepsy, seizure requiring anti-seizure medications, paresis, aphasia, stroke,
severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic
brain syndrome or psychosis. Subarachnoid hemorrhage or central nervous system (CNS)
bleed within 3 months of screening

14. Subject has active malignant tumors other than AML/MDS that requires active
antineoplastic or radiation therapy at the time of screening. Maintenance therapy or
hormonal therapy for well-controlled malignancy is allowed

15. Females who are pregnant or breastfeeding

16. Subjects with any significant medical condition, laboratory abnormality, or
psychiatric illness that would prevent the subject from participating in study (or
full access to medical records) as written including follow up, the interpretation
of data or place the subject at unacceptable risk are excluded