Phase Ib Study of CD33 FPBMC in Patients With MRD+ AML or MDS

Inclusion Criteria19

• \. Adults: ≥18 years of age 2. Diagnosis of either:
• 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.
• \. Patients with R/R MDS or R/R MDS/MPN overlap syndromes must have at least one of the following:
• Bone marrow blasts ≥ 5%
• Appearance of previously absent leukemic blasts in peripheral blood
• Absolute neutrophil count \<1 x 109/L and 50% below best unsupported on-study value
• Platelet count \<100 x 109/L and 50% below best unsupported on-study value
• Hemoglobin \<11g/dL, and ≥2 g/dL reduction from best unsupported on-study value
• Increase of the volume of transfused red blood cells by more than 30% in an 8-week period
• Increase of the number of transfused platelet units by more than 30% in an 8-week period In the case of criteria 4-8 above, no reasonable alternative explanation such as drug toxicity should be identified.
• \. Patients with AML must have persistent or recurrent MRD positivity defined by presence of blasts ≥5% AND/OR disease detected by multiparametric flow cytometry (MFC) at a level of ≥0.1%, AND/OR persistent genomic mutations other than those found most with CHIP AND/OR persistent cytogenetic abnormalities related to underlying myeloid neoplasm
• \. Residual blasts must be positive for CD33 expression at any level. Note: Patients whose most recent disease-positive evaluation by flow cytometry showed CD33 expression but whose current assessment for MRD is only positive for genomics or cytogenetics may be included.
• \. Left Ventricular Ejection Fraction (LVEF) ≥ 45% at rest (MUGA or echocardiogram)
• \. Performance status ≤ 2 (ECOG Scale)
• \. Females of childbearing potential and males must agree to use an effective method for contraception for the duration of the treatment with study drug plus 90 days (duration of sperm turnover). Males must also abstain from sperm donations during study treatment and for at least 90 days after the last dose of study drug.
• \. Ability to provide informed consent and provision of written informed consent In order to be eligible to participate in the dose expansion portion of this study, an individual must meet all criteria that apply to the R/R MDS or R/R AML population (Newly diagnosed patients and patients with MDS/MPN overlap syndromes are not eligible for the expansion phase of the study).
• In order to be eligible to participate in the dose expansion portion of this study, an individual must meet all criteria that apply to the R/R MDS or R/R AML population (Newly diagnosed patients and patients with MDS/MPN overlap syndromes are not eligible for the expansion phase of the study).