Dendritic Cell/AML Fusion Cell Vaccine Following Allogeneic Transplantation in AML Patients

NCT ID: NCT03679650

Last Updated: 2025-01-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-11
• Study Completion Date: 2026-08-31

Brief Summary

This research study is studying a cancer vaccine called Dendritic Cell/AML Fusion vaccine (DC/AML vaccine) as a possible treatment for Acute Myelogenous Leukemia (AML).

The interventions involved in this study are:

• Dendritic Cell/AML Fusion vaccine (DC/AML vaccine)
• Decitabine, a chemotherapy drug

Detailed Description

This research study is a Phase I clinical trial, which tests the safety of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. This study is investigating the DC/AML vaccine with and without the drug decitabine as a possible treatment for AML in the post-transplant setting.

The FDA (the U.S. Food and Drug Administration) has not approved the DC/AML vaccine as a treatment for any disease.

The FDA has approved decitabine as a treatment option for this disease.

The FDA has not approved the combination of the DC/AML vaccine with decitabine as a treatment option for any disease,

In this research study, the investigators are determining if the DC/AML vaccine can be used safely in subjects with acute leukemia after they have undergone a transplant, and whether the DC/AML vaccine alone is capable of producing immune responses against leukemia. Cancer cells are foreign to the body and have unique markers that distinguish them from normal cells.

These markers can potentially serve as targets for the immune system. An immune response is any reaction by the immune system; a complex system that is responsible for distinguishing us from everything foreign to us, and for protecting us against infections and foreign substances.

The DC/AML vaccine is an investigational agent that tries to help the immune system to recognize and fight against cancer cells. Unlike a standard vaccine that is used to prevent infections, cancer vaccines are being studied to see if they can fight cancers that are already in the body. Laboratory studies have shown that when dendritic cells and tumor cells are brought together, the dendritic cells can stimulate immune responses against the tumor and, in some cases, cause the tumor to shrink.

Decitabine is thought to act as an anti-metabolite. It seems to work by having a toxic effect on the abnormal bone marrow cells. It also appears to affect the DNA in genes that control cell growth. This promotes normal specialization and blood cell growth, so that the body is better able to make red blood cells, white blood cells, and platelets.

Conditions

Acute Myelogenous Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AML Patient who are undergoing allogeneic transplantation

• Patients will be vaccinated with DC/AML fusion cells
• Four days of GM-CSF given subcutaneously at the site of vaccination
• Patients will receive 2 vaccines, 3 weeks apart, with the potential for a booster vaccine
• Patients will be treated with 5 days of decitabine in the post-transplant setting

Group Type: EXPERIMENTAL

decitabine

Intervention Type: DRUG

Decitabine is thought to act as an anti-metabolite. It seems to work by having a toxic effect on the abnormal bone marrow cells.

DC/AML fusion cells

Intervention Type: BIOLOGICAL

An investigational agent that tries to help the immune system to recognize and fight against cancer cells

AML Patient who are undergoing transplantation

• Patients will be vaccinated with DC/AML fusion cells
• Four days of GM-CSF given subcutaneously at the site of vaccination
• Patients will receive 2 vaccines, 3 weeks apart, with the potential for a booster vaccine

Group Type: EXPERIMENTAL

DC/AML fusion cells

Intervention Type: BIOLOGICAL

An investigational agent that tries to help the immune system to recognize and fight against cancer cells

Interventions

decitabine

Decitabine is thought to act as an anti-metabolite. It seems to work by having a toxic effect on the abnormal bone marrow cells.

Intervention Type: DRUG

DC/AML fusion cells

An investigational agent that tries to help the immune system to recognize and fight against cancer cells

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Jacalyn Rosenblatt

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jacalyn Rosenblatt, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status: RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jacalyn Rosenblatt, MD

Role: CONTACT

jrosenb1@bidmc.harvard.edu

617-667-5982

Facility Contacts

Emma Logan, BSN

Role: primary

eklogan@bidmc.harvard.edu

617-667-5984

Robert J Soiffer, MD

Role: primary

Robert_soiffer@dfci.harvard.edu

Other Identifiers

1P50CA206963-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-202

Identifier Type: -

Identifier Source: org_study_id