Phase Ib Study of Anti-CD3 x Anti-CD33 Bispecific Antibody (CD33Bi) Armed Fresh Peripheral Blood Mononuclear Cells (CD33 FPBMC) in Patients With Measurable Residual Disease (MRD)+ Acute Myeloid Leukemia or Myelodysplastic Syndrome
Summary
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.
Detailed description
Once subjects are determined to be eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure. The T cells in the mononuclear cells are coated with bispecific antibody to activate the T cells and the mononuclear cells are reinfused into the patients so the T cells can multiply and kill AML/MDS cells. At least 72 hours after the leukapheresis procedure, study treatment will start. 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. After about 2 cycles of study treatment, participants will have another leukapheresis procedure. Before, throughout and following study treatment, research blood will be collected to better understand immune response. Disease status will be checked regularly during and after study treatment.
Arms & interventions
- DrugCD33 FPBMC
Participants 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.
Outcome measures
Primary
DLTs
Escalation phase participants only
Time frame: From start of treatment through 7 days after the 4th infusion (for each participant)
Secondary
Overall response rate (ORR)
Time frame: During study treatment and for up to 3 years following intervention
Disease status
Time frame: During study treatment and for up to 3 years following intervention
Progression free survival (PFS)
Time frame: From baseline to disease progression or death from any cause, whichever comes first, assessed up to 3 yrs after last study drug administration
Adverse Events (AEs)
Time frame: During and up to 30 days after last study treatment (all reportable AEs) and during long term follow-up (up to 3 years) for serious AEs considered related to study treatment
Eligibility criteria
Study locations (1)
University of Virginia
Charlottesville, Virginia, 22908