Personalized T-cell therapy with a DC/AML fusion vaccine plus decitabine and venetoclax for AML

A Phase 1, First in Human Study of Adoptive T Cell Therapy With T Cells Stimulated by Dendritic Cell (DC)/Tumor Fusions in Combination With Decitabine and Venetoclax in Patients With Acute Myeloid Leukemia (AML)

This will try combining a personalized T-cell therapy and a DC/AML fusion vaccine with decitabine and venetoclax for people with newly diagnosed or relapsed AML to see if it is safe and can boost anti-leukemia immunity.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sex: All
• Sponsor: Beth Israel Deaconess Medical Center (other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT07374029 on ClinicalTrials.gov

What this trial studies

This is a phase I dose-escalation trial testing first-in-human DC/AML primed T cells together with a DC/AML fusion vaccine, GM-CSF, and the standard agents decitabine and venetoclax in patients with newly diagnosed or first-relapse AML. Participants will undergo tumor (leukemia) collection to create the personalized vaccine and T cells, receive decitabine and venetoclax as backbone therapy, and then get the experimental immune products with careful safety monitoring. The main goals are to determine feasibility, tolerability, and immune and clinical signals, with serial laboratory and clinical assessments. About 30 participants are expected to enroll at Beth Israel Deaconess Medical Center with staged dose escalation and follow-up for safety and immune responses.

Who should consider this trial

Good fit: Ideal candidates are adults with newly diagnosed or first-relapse AML for whom decitabine plus venetoclax is appropriate, with ECOG performance status 0–2 and adequate organ and marrow function.

Not a fit: Patients with poor organ function, uncontrolled infections, prior treatments making decitabine/venetoclax inappropriate, or very advanced refractory disease may not receive benefit from this approach.

Why it matters

Potential benefit: If successful, the combination could strengthen AML-specific immune responses and potentially increase remission duration or rates compared with standard therapy alone.

How similar studies have performed: Decitabine plus venetoclax is an established regimen for AML, but DC/AML fusion vaccines and DC/AML-primed T cells are first-in-human and therefore novel with no prior human efficacy data.

Eligibility criteria

Inclusion Criteria Prior to Tumor Collection

* 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.

Exclusion Criteria Prior to Tumor Collection

* 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.

Inclusion Criteria Prior to Leukapheresis

* 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

Exclusion Criteria Prior to Leukapheresis

* Patients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, ischemic coronary disease or congestive heart failure
* Patients who, with their treating physician, choose to proceed with an allogeneic transplant at the time of remission will not be eligible for leukapheresis
* 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 permitted.
* Current or prior use of immunosuppressive medication within 14 days prior to first T cell infusion. The following are exceptions to this criterion: intranasal, inhaled, topical or local steroid injections (eg. intra-articular injection); steroids as premedication for hypersensitivity reactions; systemic corticosteroid at physiologic doses not to exceed 10mg/day of prednisone or equivalent
* Known human immunodeficiency virus (HIV), untreated hepatitis C virus (HCV) or evidence of active hepatitis B virus (HBV).
* Female subjects who are pregnant, breast-feeding or female patients of reproductive potential who are not employing an effective method of birth control from starting treatment, including dosing interruptions through 90 days after last dose of treatment. Refrain from egg cell donation while receiving vaccination and for at least 90 days after the last dose of treatment.
* Male subjects who are not employing an effective method of birth control from starting vaccine, including dosing interruptions through 90 days after receipt of the last dose of treatment. Refrain from sperm cell donation while receiving vaccination and for at least 90 days after the last dose of treatment.

Inclusion Criteria Prior to Treatment with DC/AML Primed T cells and DC/AML fusion vaccine

* Patient completed 4 cycles of decitabine and venetoclax without evidence of disease recurrence or progression
* Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0, other than grade 3 anemia, at the time of initiation of cycle 5, 6, or 7 of decitabine/venetoclax therapy.
* 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
* Generation of adequate yield of T cells to meet dosing requirement

Where this trial is running

Boston, Massachusetts

• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: David Avigan, MD — Beth Israel Deaconess Medical Center
• Study coordinator: David Avigan, MD

Conditions: Acute Myeloid Leukemia, Acute Myeloid Leukemia, in Relapse, Newly Diagnosed Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia