Clinical Trials

Inclusion Criteria:

- Participants must be diagnosed with either relapsed or refractory AML (including extramedullary disease), MRD-positive AML, or higher risk MDS.

- Absolute lymphocyte count ≥ 0.2 k/µL.

- Karnofsky performance status score ≥ 60%.

- Life expectancy ≥ 12 weeks from the time of enrollment.

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

- Bilirubin ≤ 2.0 mg/dL or total bilirubin ≤ 3.0 x ULN 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 ULN.

- 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. Note: Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for at least 1 year
following study treatment (T cell infusion); should a woman participant or female partner of a male participant become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.

- Participant has a matched bone marrow donor and is otherwise able to receive a bone marrow transplant (dose escalation phase only and for participants with MRD-positive
AML)

- Participants who have undergone allo-SCT and/or donor lymphocyte infusion (DLI) are eligible if they are at least 3 months post SCT, prior to apheresis, atleast 30 days
post last DLI prior to apheresis, have not received treatment or prophylaxis for GVHD 6 weeks before administration of CAR T cells, 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 (APL M3): t(15;17)(q22;q12); (promyelocytic leukemia [PML]/retinoic acid receptor [RAR] alpha [a]) and variants excluded.

- Participants with peripheral blood blasts > 35%

- 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 ( i.e., no blasts in cerebrospinal fluid [CSF] by cytology and flow cytometry) will be eligible.

- Prior treatment with investigational CD33 targeting CAR T therapy for any disease.

- Prior treatment with licensed or investigational CD33 targeting monoclonal antibody or antibody drug conjugate within 6 months of apheresis.

- Participants enrolled in another investigational therapy protocol for their disease within 14 days or 5 half-lives of apheresis, 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 (e.g., cervix) may enroll irrespective of the time of diagnosis.

- Pregnant and lactating women are excluded from this study.

- 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).

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

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/29/23. Questions regarding updates should be directed to the study team contact.