Cancer vaccine for treating Acute Myelogenous Leukemia after transplantation

A Phase I Clinical Trial of Dendritic Cell/AML Fusion Cell Vaccine Alone and in Conjunction With Decitabine Following Allogeneic Transplantation in AML Patients

This study is testing a new cancer vaccine to see if it can help people with Acute Myelogenous Leukemia feel better after they have had a stem cell transplant.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beth Israel Deaconess Medical Center (Academic / other)
• Drugs / interventions: prednisone, chemotherapy
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT03679650 on ClinicalTrials.gov

What this trial studies

This Phase I clinical trial is investigating the safety and efficacy of a Dendritic Cell/AML Fusion vaccine (DC/AML vaccine) as a treatment for Acute Myelogenous Leukemia (AML) in patients who have undergone allogeneic transplantation. The study will assess the vaccine's ability to elicit immune responses against leukemia cells, potentially improving patient outcomes. Participants will receive the vaccine with or without the chemotherapy drug decitabine, which is already FDA-approved for AML. The trial aims to determine if this combination can safely enhance the immune response in AML patients post-transplant.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with AML who have undergone allogeneic transplantation and meet specific health criteria.

Not a fit: Patients who have not undergone allogeneic transplantation or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel immunotherapy option for AML patients, potentially improving survival rates and quality of life.

How similar studies have performed: While the DC/AML vaccine is investigational, similar immunotherapy approaches have shown promise in other studies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Patients with AML who have undergone AML cell harvest and cryopreservation as per protocol 16-593 or companion protocol 18-232.
* Patients must have had a minimum of 5x107 cells cryopreserved.
* Patients must be day 25-45 following allogeneic transplantation from either:

  * Group A: HLA 8/8 or 7/8 matched related donor or HLA 8/8 matched unrelated donor, as determined by antigen or allele level typing at HLA A,B,C, and HLA DRB1.

OR

* Group B: Haplo-identical donor

  * Patients must be ≥ 18 years old
  * ECOG performance status ≤2 (Appendix A)
  * Participants must have normal organ and marrow function as defined below:
* Total bilirubin ≤ 2.0 mg/dL (unless patient has Gilbert's disease)
* AST(SGOT)/ALT(SGPT) ≤ 3 × institutional upper limit of normal
* Creatinine ≤ 2.0 mg/dl
* Absolute neutrophil count \> 1000
* Platelet count \> 50,000

  * The effects of DC/AML fusion 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.
  * No evidence of ongoing grade 2 or higher aGVHD
  * Must be on prednisone \<20mg or other steroid equivalent
  * Donor chimerism of bone marrow \>60%
  * Resolution of all transplant related grade III-IV toxicity as per CTC criteria 4.0
  * Complete remission defined by absence of circulating blasts and less than 5% blasts in the bone marrow
  * Ability to understand and the willingness to sign a written informed consent document.

Eligibility Prior to Initiating Vaccination (Groups A and B)

* Assessments to be done between Day 45-75 post-transplant.
* At least 2 doses of fusion vaccine were produced
* No ongoing grade II-IV acute GVHD
* Prednisone requirement of \< 20mg a day or steroid equivalent
* Participants must have normal organ and marrow function as defined below:

  * Total bilirubin ≤ 2.0 mg/dL (unless patient has Gilbert's disease)
  * AST(SGOT)/ALT(SGPT) ≤ 3 × institutional upper limit of normal
  * Creatinine ≤ 2.0 mg/dl
  * Absolute neutrophil count \> 1000
  * Platelet count \> 50,000
* No uncontrolled acute infection
* No CTCAE grade ≥ 3 non-hematologic toxicity
* No serious intercurrent illness such as active acute infection, or significant cardiac disease characterized by clinically significant arrhythmia, active ischemic coronary disease or symptomatic congestive heart failure.
* Participants must be in a complete remission

Pre-Treatment Criteria Prior to Decitabine (Group A Cohort 2)

* Assessments to be done within 3 days prior to initiation of therapy.
* Participants must have normal organ and marrow function as defined below:
* Total bilirubin ≤ 2.0 mg/dL (unless patient has Gilbert's disease)

  * AST(SGOT)/ALT(SGPT) ≤ 3 × institutional upper limit of normal
  * Creatinine ≤ 2.0 mg/dl
  * Absolute neutrophil count \> 1000
  * Platelet count \> 50,000

Exclusion Criteria:

* Because of compromised cellular immunity, patients with a known history of HIV are excluded
* Leukemia with active CNS involvement
* 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.
* Participants may not be receiving any other Non-FDA approved study agents at the start of vaccination
* Uncontrolled intercurrent illness including uncontrolled active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness that would limit compliance with study requirements.
* Autoimmune or inflammatory disorders requiring active treatment with systemic steroids or immunosuppressive therapy limited to the following:

  * GI Disorders: (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\]
  * Systemic lupus erythematosus
  * Wegener's syndrome \[granulomatosis with polyangiitis\]
  * Myasthenia gravis
  * Graves' disease
  * Rheumatoid arthritis
  * Hypophysitis
  * Uveitis

Where this trial is running

Boston, Massachusetts and 1 other locations

• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Jacalyn Rosenblatt, MD — Beth Israel Deaconess Medical Center
• Study coordinator: Jacalyn Rosenblatt, MD

Conditions Acute Myelogenous Leukemia; AML