PRGN-3006 Adoptive Cellular Therapy Relapsed or Refractory CD33-Positive AML or High Risk MDS

This is a single center, nonrandomized, investigator-initiated Phase 1/1b safety and
tolerability study. The safety and tolerability of PRGN-3006 T cells will be assessed
following intravenous administration of escalating doses in patients with relapsed or
refractory CD33-positive acute myeloid leukemia (AML) or higher risk myelodysplastic
syndromes (MDS).

The study will enroll in two phases: an initial dose escalation phase followed by a dose
expansion phase.

Inclusion Criteria:

- Participants must be diagnosed with either relapsed or refractory CD33+ AML or higher
risk MDS

- Absolute lymphocyte count ≥ 0.2 k/μL.

- Karnofsky performance status score ≥60%.

- Life expectancy 12 weeks or more from the time of enrollment.

- Pretreatment calculated or measured creatinine clearance (absolute value) of ≥ 40
mL/minute or Cr > 2x upper limit of normal (ULN).

- Serum bilirubin ≤ 2.0 mg/dL or total bilirubin ≤ 3.0 x IULN with direct bilirubin
within normal range in Participants with well documented Gilbert's syndrome or
hemolysis or who require regular blood transfusions

- Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 3.0 x IULN.

- Ejection fraction measured by echocardiogram (ECHO) or multi gated acquisition scan
(MUGA) > 45%.

- Participant does not require supplemental oxygen or mechanical ventilation AND has an
oxygen saturation by pulse oximetry of ≥ 92% or higher on room air.

- Negative serum pregnancy test.

- Participant has a matched bone marrow donor and is otherwise able to receive a bone
marrow transplant (dose escalation part only)

- Participants who have undergone allo-SCT are eligible if they are at least 3 months
post SCT, have relapsed AML/MDS as defined above, are not on treatment or prophylaxis
for GVHD for at least 6 weeks before administration of CAR T cells, and have no active
GVHD.

- All Participants must have the ability to understand and willingness to sign a written
informed consent.

Exclusion Criteria:

- Diagnosis of acute promyelocytic leukemia

- Participants with extramedullary disease as their sole site of relapsed AML.

- Known central nervous system (CNS) leukemic involvement that is refractory to
intrathecal chemotherapy and/or cranio-spinal radiation; Participants with a history
of CNS disease that have been effectively treated to complete remission will be
eligible.

- Prior treatment with investigational CAR-T therapy for any disease.

- Participants enrolled in another investigational therapy protocol for AML within 14
days or 5 half-lives of enrollment, whichever is shorter.

- Ongoing uncontrolled serious infection, symptomatic congestive heart failure, unstable
angina pectoris, uncontrolled cardiac arrhythmia, poorly controlled pulmonary disease
or psychiatric illness/social situations that would limit compliance with study
requirements.

- Human immunodeficiency virus (HIV) seropositivity, or active hepatitis B or C
infection based on testing performed within 28 days of enrollment.

- Participants requiring agents other than hydroxyurea to control blast counts within 14
days of study enrollment.

- Participants with presence of other active malignancy within 1 year of study entry.

- Participants with adequately resected basal or squamous cell carcinoma of the skin, or
adequately resected carcinoma in situ may enroll irrespective of the time of
diagnosis.

- Pregnant and breastfeeding women.

- History of allergic reactions attributed to compounds of similar chemical or
biological composition to cetuximab (anti-EGFR).

- Active autoimmune disease requiring systemic immunosuppressive therapy (i.e. > 10mg of
prednisone daily or equivalent).

- Participants who, in the opinion of the investigator, may not be able to comply with
the safety monitoring requirements of the study.