Acute Myeloid LeukemiaPhase 1AML-MDS 001NCT07270978
Phase Ib Study of CD33 FPBMC in Patients With MRD+ AML or MDS
A Phase 1 study testing CD33 FPBMC in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Virginia at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm
- What is being tested?
- CD33 FPBMC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Mar 2026to Jul 2031
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 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.
- 4. Patients with R/R MDS or R/R MDS/MPN overlap syndromes must have at least one of the following:
- Bone marrow blasts ≥ 5%
Show all 19Show fewer
- 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.
- 5. 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
- 6. 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.
- 7. Left Ventricular Ejection Fraction (LVEF) ≥ 45% at rest (MUGA or echocardiogram)
- 8. Performance status ≤ 2 (ECOG Scale)
- 9. 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.
- 10. 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).
Who cannot join
- 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)
Show all 17Show fewer
- 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
- 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.
- Known allergy to hypomethylating agents
- Blasts ≥ 25%
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Ashley Donihee, 434-243-6377, zwz6jm@uvahealth.org
Avani Hopkins, 434-243-8108, AJH7JQE@uvahealth.org
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm
- Being tested
- CD33 FPBMC
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD33 FPBMCDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: CD33 FPBMC |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLTs
Escalation phase participants only
Measured: From start of treatment through 7 days after the 4th infusion (for each participant)
Secondary outcomes (4)
Overall response rate (ORR)
Based on MRD status (AML cohort) and IWG criteria1 (MDS cohort)
Measured: During study treatment and for up to 3 years following intervention
Disease status
According to European LeukemiaNet (ELN) criteria (AML cohort) or IWG criteria (MDS cohort)
Measured: During study treatment and for up to 3 years following intervention
Progression free survival (PFS)
European LeukemiaNet (ELN) criteria (AML cohort) or IWG criteria (MDS cohort)
Measured: 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)
According to CTCAE v5
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2025
- Study start26 Mar 2026
- Primary completionAug 2028 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel R. Reed, University of Virginia
- Investigators
- Daniel Reed, MD, Principal investigator, Assistant ProfessorLawrence Lum, MD, DSc, Study director, IND Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07270978
- Sponsor's protocol ID
- 302332
- Acronym
- AML-MDS 001
- Status last verified
- May 2026
- First submitted
- 17 Nov 2025
- Last updated
- 11 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07270978
- Acronym / sponsor ID
- AML-MDS 001 / 302332
- Conditions
- Acute Myeloid Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasm
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 23 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 26 Mar 2026 (actual)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Jul 2031 (estimated)
- First posted
- 8 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD33 FPBMC + hypomethylating agent with or without venetoclax | Experimental | Drug: CD33 FPBMC4 weekly infusions of CD33 fresh peripheral blood mononuclear cells (FPBMC) followed by 4-6 weeks of hypomethylating agent with/without venetoclax. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
- 4. Patients with R/R MDS or R/R MDS/MPN overlap syndromes must have at least one of the following:
- 5. 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
Key exclusion criteria (17 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD33 FPBMCParticipants 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. | Drug | CD33 FPBMC + hypomethylating agent with or without venetoclax |
Primary outcome
DLTs
Time frame: From start of treatment through 7 days after the 4th infusion (for each participant)
Escalation phase participants only
4 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 May 2026.
- Individual participant dataSharing planned: No
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel Reed, MD principal investigator
Assistant Professor
Lawrence Lum, MD, DSc study director
IND Sponsor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD33 FPBMC in people with Acute Myeloid Leukemia and Myelodysplastic Syndromes, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ashley Donihee (434-243-6377, zwz6jm@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLTs (time frame: From start of treatment through 7 days after the 4th infusion (for each participant)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.