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

NCT07270978 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 302332
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm; Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• DLTs

  Escalation phase participants only

  From start of treatment through 7 days after the 4th infusion (for each participant)

Secondary Outcomes (4)

• Overall response rate (ORR)

  During study treatment and for up to 3 years following intervention

• Disease status

  During study treatment and for up to 3 years following intervention

• Progression free survival (PFS)

  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)

  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

Study Arms (1)

CD33 FPBMC + hypomethylating agent with or without venetoclax

EXPERIMENTAL

4 weekly infusions of CD33 fresh peripheral blood mononuclear cells (FPBMC) followed by 4-6 weeks of hypomethylating agent with/without venetoclax.

Drug: CD33 FPBMC

Interventions

CD33 FPBMC DRUG

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.

CD33 FPBMC + hypomethylating agent with or without venetoclax

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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)

You may not qualify if:

• 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
• Clinically significant organ dysfunction, defined as any of the following:
• AST or ALT \>3x the upper limit of normal (ULN)
• Total bilirubin \>1.5x the ULN, unless due to ongoing hemolysis or Gilbert's syndrome, in which case \> 3.0 mg/dL
• Absolute lymphocyte count (ALC) \< 300 lymphocytes/microliter
• Creatinine clearance \<30 mL/min
• Active serious infection not controlled by oral or intravenous antibiotics (e.g. persistent fever or lack of clinical improvement despite antimicrobial treatment).
• Known human immunodeficiency virus (HIV) with detectable viral load.
• Known hepatitis B surface antigen seropositive or known or suspected active hepatitis C infection
• a. Note: Patients who have isolated positive hepatitis B core antibody (ie, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load. Patients who have positive hepatitis C antibody may be included if they have an undetectable hepatitis C viral load.
• Patients with a prior or concurrent malignancy whose natural history or treatment is anticipated to interfere with the safety or efficacy assessment of the investigational regimen (according to the treating investigator).
• Treatment with any antileukemic agents or chemotherapy (other than hypomethylating agents or venetoclax) agents in the last 7 days or 5 half-lives (whichever is sooner) before study entry. Note: treatment with hydroxyurea may continue through the first cycle of study treatment.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Daniel Reed, MD

  Assistant Professor

  PRINCIPAL INVESTIGATOR

• Lawrence Lum, MD, DSc

  IND Sponsor

  STUDY DIRECTOR

Central Study Contacts

Ashley Donihee

CONTACT

434-243-6377; zwz6jm@uvahealth.org

Avani Hopkins

CONTACT

434-243-8108; AJH7JQE@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: December 8, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)