The purpose of this study is to understand the safety and estimate the efficacy of combining anti-CD3 x anti-CD33 bispecific antibody (CD33Bi) armed fresh peripheral blood mononuclear cells (CD33Bi FPBMC) for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) where they still have detectable disease ("MRD+") after some treatment. Participants receive 4 weekly doses of CD33 FPBMC by intravenous infusion followed by 4-6 weeks of standard treatment with a hypomethylating agent (type of treatment such as decitabine or azacitidine) and possibly a drug called venetoclax. This is considered 1 cycle of study treatment and may be repeated up to 4 times during the study.
Newly diagnosed or relapsed/refractory AML who have received either intensive induction chemotherapy or at least 2 cycles of a non-intensive options such as hypomethylating agent and venetoclax or other targeted agent
Relapsed/ refractory (R/R) MDS who have received at least 2 prior cycles of hypomethylating agent and venetoclax or single agent hypomethylating agent for at least 4 cycles
Relapsed/refractory (R/R) MDS/MPN overlap syndromes like CMML who have received at least 2 prior cycles of azacitidine and venetoclax or single agent hypomethylating agent for at least 4 cycles 3. For patients with targetable mutations (IDH1, IDH2, KMT2A, or FLT3): Receipt of and/or decision not to receive associated inhibitor.
Bone marrow blasts ≥ 5%
Pregnancy or lactation
Prior treatment with anti-CD33 therapy
Patients who are being actively considered for stem cell transplant, unless participation in the study prior to the planned stem cell transplant is considered to be in the best interest of the patient in the opinion of the treating investigator in consultation with the transplant team. This does not exclude patients that may be eligible for stem cell transplant at some future (undetermined) date.
Past hematopoietic stem cell transplant (HSCT) with graft vs host disease requiring systemic immunosuppression other than low dose prednisone (10 mg) (or the equivalent dose of another immunosuppressant) within the 4 weeks before registration
Single group
CD33 FPBMC
DrugParticipants will receive up to 4 cycles of 4 weekly infusions of CD33 infusions followed by 4-6 weeks of a hypomethylating agent with or without venetoclax according to standard clinical care.
DLTs
Escalation phase participants only
Overall response rate (ORR)
Based on MRD status (AML cohort) and IWG criteria1 (MDS cohort)
Disease status
According to European LeukemiaNet (ELN) criteria (AML cohort) or IWG criteria (MDS cohort)
Progression free survival (PFS)
European LeukemiaNet (ELN) criteria (AML cohort) or IWG criteria (MDS cohort)
Adverse Events (AEs)
According to CTCAE v5
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