Adoptive T Cell Therapy With DC/AML Fusion Vaccine Plus Decitabine and Venetoclax in AML

NCT07374029 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-593
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this research study is to test if the combination of a new T cell therapy (dendritic cell (DC) / acute myeloid leukemia (AML) primed T cells), vaccine (DC/AML fusion vaccine) and standard of care decitabine and venetoclax is feasible and safe and effective for treatment of acute myeloid leukemia (AML). The names of the study drugs involved in this study are:

• DC/AML fusion vaccine (immune cell vaccine)
• Granulocyte-macrophage colony-stimulating factor (GM-CSF) (a type of growth factor or hormone)
• DC/AML Primed T cells (immune cells)
• Decitabine (a type of chemotherapy drug)
• Venetoclax (a type of antineoplastic agent)

Conditions

Acute Myeloid Leukemia; Acute Myeloid Leukemia, in Relapse

Keywords

Acute Myeloid Leukemia (AML); Newly Diagnosed Acute Myeloid Leukemia (AML); Relapsed Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (3)

• Successful Manufacture and Administration Rate of Vaccine-Educated T Cells

  Successful manufacture and administration rate is defined as the proportion of enrolled participants for whom autologous vaccine-educated T cells are successfully manufactured and administered per protocol.

  28 weeks

• Maximum Tolerated Dose (MTD) of Vaccine-Educated T Cells

  The MTD is defined as the highest dose level that one or fewer participants experiences a dose-limiting toxicity (DLT) or one dose level below the maximum administered dose level where two or more participants experience a DLT.

  56 Days

• Toxicity Rate of Vaccine-Educated T Cells, Including CRS, Neurotoxicity, and Infections

  Toxicity rate of vaccine-educated T cells is defined as the proportion of participants who experience at least one toxicity, including cytokine release syndrome, neurotoxicity, or infections, out of all participants who receive at least one T-cell infusion.

  5 years

Secondary Outcomes (4)

• Relapse-Free Survival (RFS) at 1 Year Post Administration of Vaccine Educated T Cells

  1 year

• Relapse-Free Survival (RFS) at 2 Years Post Administration of Vaccine Educated T Cells

  2 years

• MRD Negative Conversion Rate

  MRD samples are collected up to 6 months after the last cell therapy dose.

• Median Overall Survival (OS)

  5 years

Study Arms (2)

Adoptive T cell therapy with DC/AML fusion vaccine, decitabine, and venetoclax

EXPERIMENTAL

* Baseline visit * Cycles 1 - 2 (28-day cycles): * Days 1 - 5: predetermined dose of Decitabine 1x daily * Days 1 - 21: predetermined dose of Venetoclax 1x daily * Bone marrow biopsy and aspiration at end of Cycle 2 * Leukapheresis * Cycles 3 - 4 (28-day cycles): * Days 1 - 5: predetermined dose of Decitabine 1x daily * Days 1 - 21: predetermined dose of Venetoclax 1x daily

Drug: Decitabine; Drug: Venetoclax

Dose-Escalation

EXPERIMENTAL

A standard 3+3 dose escalation design will be used to find the maximum tolerated dose (MTD) of T cells. If less than 1 out of 3 or less than 2 out of 6 participants experience a dose-limiting toxicity (DLT) in a given cohort then escalation will proceed to the next dosing level. If 2 out of 6 participants experience a DLT then the prior dose level will be defined as the MTD. An additional 12 participants will be treated at the MTD. -Cycles 5 - 7 (42-day cycles): * Days 1 - 5: predetermined dose of Decitabine 1x daily * Day 15: predetermined dose of DC/AML Primed T cells 1x daily * Days 1 - 14: predetermined dose of Venetoclax 1x daily * Day 29: predetermined dose of DC/AML fusion vaccine 1x daily * Day 29: predetermined dose of GM-CSF 1x daily Follow up visits monthly for 6 months Longer term follow up every 3 months for 2 years then yearly for 3 years

Biological: DC/AML Fusion Vaccine; Biological: T-Cell Therapy; Drug: Decitabine; Drug: Venetoclax; Drug: GM-CSF

Interventions

Decitabine DRUG

A pyrimidine nucleoside analogue, via intravenous infusion, per standard of care.

Adoptive T cell therapy with DC/AML fusion vaccine, decitabine, and venetoclax; Dose-Escalation

DC/AML Fusion Vaccine BIOLOGICAL

Autologous fusion vaccine of dendritic cells and AML cells, via subcutaneous injection (under the skin) per standard of care.

Dose-Escalation

T-Cell Therapy BIOLOGICAL

Autologous adoptive T cells, via intravenous (into the vein) infusion, per protocol.

Dose-Escalation

Venetoclax DRUG

A BCL-2 inhibitor, taken orally per standard of care.

Adoptive T cell therapy with DC/AML fusion vaccine, decitabine, and venetoclax; Dose-Escalation

GM-CSF DRUG

A Granulocyte-Macrophage Colony-Stimulating Factor, via subcutaneous injection, per standard of care.

Dose-Escalation

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have AML at initial diagnosis for which decitabine/venetoclax is planned as standard of care therapy. This can include patients with IDH or FLT-3 mutations for whom the addition of targeted therapy agents directed at IDH or FLT-3 mutations to the decitabine/venetoclax regimen is preferred per the treating physician.
• Patients with AML in first relapse after cytotoxic and/or targeted therapy for which decitabine and venetoclax therapy is appropriate standard of care. This can include patients with IDH or FLT-3 mutations for whom the addition of targeted therapy agents directed at IDH or FLT-3 mutations to the decitabine/venetoclax regimen is preferred per the treating physician.
• ECOG performance status ≤ 2 (Appendix A)
• Participants must have normal organ and marrow function as defined below:
• total bilirubin≤ 2.0 mg/dL
• AST/ALT ≤ 3 × institutional upper limit of normal
• creatinine ≤ 2.0 mg/dl
• The effects of vaccine stimulated T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients diagnosed with acute promyelocytic leukemia
• Patients treated at initial diagnosis who are appropriate for intensive induction therapy.
• Patients with active systemic autoimmune disease requiring ongoing systemic therapy are excluded. The following is an exception to this criterion: subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement. Patients with paraneoplastic auto-immune manifestations related to AML are allowed.
• Patients who have received a prior allogeneic transplant will be excluded.
• Because of compromised cellular immunity, patients who have active human immunodeficiency virus (HIV), untreated hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV).
• Patients must not have active significant cardiac disease characterized by symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia.
• Patients must not be pregnant. All premenopausal patients will undergo pregnancy testing. Men will agree to not father a child while on protocol treatment. Men and women will practice effective birth control while receiving protocol treatment.
• Patients must have obtained a response of PR or better to decitabine and venetoclax as defined in Section 11.
• Resolution of all HMA/venetoclax related grade III-IV toxicity as per CTC criteria 4.0, other than grade 3 anemia.
• Laboratories:
• ANC ≥ 1,000/µL
• Platelets ≥ 50,000/uL
• Bilirubin ≤ 2.0 mg/dL
• Creatinine ≤ 2.0 mg/dL
• AST/ALT ≤ 3.0 x ULN

Sponsors & Collaborators

• David Avigan: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Immunotherapy, Adoptive; Decitabine; venetoclax; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• David Avigan, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Avigan, MD

CONTACT

617-667-9920; davigan@bidmc.harvard.edu

Emma Logan, MSN

CONTACT

617-667-9920; eklogan@bidmc.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: January 21, 2026
• First Posted: January 28, 2026
• Study Start: February 12, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Locations

US (1)