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

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.

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