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Dendritic Cell / AML Fusion Cell Vaccine with or without Decitabine in Treating Patients with Acute Myeloid Leukemia Undergoing Donor Stem Cell Transplant

Trial Status: Active

This phase I trial studies the side effects of dendritic cell / acute myeloid leukemia (AML) fusion cell vaccine with or without decitabine in treating patients with acute myeloid leukemia undergoing donor stem cell transplant. Vaccines made from a person's cancer cells may help the body build an effective immune response to kill cancer cells. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving dendritic cell / AML fusion cell vaccine and decitabine may work better than dendritic cell / AML fusion cell vaccine alone in treating patients with acute myeloid leukemia.

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 1 x 10^7 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 ** Note: Participants who do not meet eligibility by day 45 post-transplant may be evaluated for eligibility to be enrolled to the study up to day 70 post-transplant, with approval from the overall principal investigator
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Total bilirubin =< 2.0 mg/dL (unless patient has Gilbert’s disease)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x 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 acute (a)GVHD
  • Must be on prednisone < 20 mg or other steroid equivalent
  • Donor chimerism of bone marrow >= 60%
  • Resolution of all transplant related grade 3-4 toxicity as per Common Terminology Criteria for Adverse Events (CTCAE) 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
  • Prior to Initiating Vaccination: At least 2 doses of fusion vaccine were produced
  • Prior to Initiating Vaccination: No ongoing grade II-IV acute GVHD
  • Prior to Initiating Vaccination: Prednisone requirement of < 20 mg a day or steroid equivalent
  • Prior to Initiating Vaccination: Total bilirubin =< 2.0 mg/dL (unless patient has Gilbert’s disease)
  • Prior to Initiating Vaccination: AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal
  • Prior to Initiating Vaccination: Creatinine =< 2.0 mg/dl
  • Prior to Initiating Vaccination: Absolute neutrophil count > 1000
  • Prior to Initiating Vaccination: Platelet count > 50,000
  • Prior to Initiating Vaccination: No uncontrolled acute infection
  • Prior to Initiating Vaccination: No CTCAE grade >= 3 non-hematologic toxicity
  • Prior to Initiating Vaccination: 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
  • Prior to Initiating Vaccination: Participants must be in a complete remission
  • Prior to Initiating Vaccination: Calcineurin inhibitor will be tapered
  • Prior to Initiating Booster Vaccine: 30-60 days following withdrawal of immune suppression
  • Prior to Initiating Booster Vaccine: No evidence of chronic GVHD
  • Prior to Initiating Booster Vaccine: No ongoing need for systemic steroids, with the exception of physiologic replacement doses for adrenal insufficiency
  • Prior to Initiating Booster Vaccine: Total bilirubin =< 2.0 mg/dL (unless patient has Gilbert’s disease)
  • Prior to Initiating Booster Vaccine: AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal
  • Prior to Initiating Booster Vaccine: Absolute neutrophil count > 1000
  • Prior to Initiating Booster Vaccine: Platelet count > 50,000 unsupported by transfusion
  • Prior to Initiating Booster Vaccine: No uncontrolled acute infection
  • Prior to Initiating Booster Vaccine: No CTCAE grade >= 3 non-hematologic toxicity
  • Pre-Treatment Criteria Prior to Decitabine (Group A Cohort 2): Total bilirubin =< 2.0 mg/dL (unless patient has Gilbert’s disease) (within 3 days prior to initiation of therapy)
  • Pre-Treatment Criteria Prior to Decitabine (Group A Cohort 2): AST(SGOT)/ALT(SGPT) =< 3 x institutional upper limit of normal (within 3 days prior to initiation of therapy)
  • Pre-Treatment Criteria Prior to Decitabine (Group A Cohort 2): Creatinine =< 2.0 mg/dl (within 3 days prior to initiation of therapy)
  • Pre-Treatment Criteria Prior to Decitabine (Group A Cohort 2): Absolute neutrophil count > 1000 (within 3 days prior to initiation of therapy)
  • Pre-Treatment Criteria Prior to Decitabine (Group A Cohort 2): Platelet count > 50,000 (within 3 days prior to initiation of therapy)

Exclusion Criteria

  • Because of compromised cellular immunity, patients with a known history of human immunodeficiency virus (HIV) are excluded
  • Leukemia with active central nervous system (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-Food and Drug Administration (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 including but not limited to the following: * Gastrointestinal (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 * The following are exceptions to this criterion: subjects with vitiligo or alopecia; subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement; or subjects with psoriasis not requiring systemic treatment

Massachusetts

Boston
Beth Israel Deaconess Medical Center
Status: ACTIVE
Contact: Jacalyn M. Rosenblatt
Brigham and Women's Hospital
Status: ACTIVE
Contact: Robert Jon Soiffer
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Robert Jon Soiffer

PRIMARY OBJECTIVE:

I. To assess vaccine-associated toxicity, including the incidence of acute graft-versus-host disease (GVHD).

SECONDARY OBJECTIVE: CORRELATIVE

I. To determine the immunologic response following post-transplant vaccination with respect to the presence of leukemia-reactive T cells, T cells targeting previously identified leukemia- associated antigens, T cell clonality, myeloid-derived suppressor cell (MDSC) burden, T regulatory cells, and PD-1 expressing T cells.

SECONDARY OBJECTIVE: CLINICAL

I. To assess the effect of vaccination on relapse-free survival (RFS).

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I: Between 45-75 days post standard of care transplant, patients receive autologous AML/dendritic cell (DC) fusion vaccine subcutaneously (SC) at weeks 1 and 4. Patients may receive one booster vaccine at 6-9 months post-transplant.

COHORT II: Patients receive autologous AML/DC fusion vaccine as in Cohort I. Patients also receive decitabine intravenously (IV) continuously over 5 days during week 3 (12-16 days post the first dose of vaccine).

After completion of study treatment, patients are followed up every 3 months for 2 years, and then yearly for 5 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Jacalyn M. Rosenblatt

  • Primary ID 18-202
  • Secondary IDs NCI-2018-02404
  • Clinicaltrials.gov ID NCT03679650