This research study is a Phase II clinical trial. Phase II clinical trials test the safety
and effectiveness of an investigational intervention to learn whether the intervention works
in treating a specific disease. "Investigational" means that the intervention is being
studied.
The FDA (the U.S. Food and Drug Administration) has not approved the DC/AML vaccine as a
treatment for any disease.
The FDA (the U.S. Food and Drug Administration) has not approved durvalumab as a treatment
for AML.
In this research study, the investigators are determining if the DC/AML vaccine can be used
safely in subjects with acute leukemia after finishing chemotherapy, and whether the DC/AML
vaccine is capable of producing immune responses against leukemia alone. 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 Dendritic Cell Fusion 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.
Step 1: Eligibility Criteria for Tumor Collection
Inclusion Criteria
- Patients must have AML at initial diagnosis or at first relapse
- Patients must be ≥ 55 years old
- ECOG performance status ≤2 (Appendix A)
- Patients must have normal organ and marrow function as defined below:
total bilirubin ≤ 2.0 mg/dL AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal
creatinine ≤ 2.0 mg/dl
- 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.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
-Active or prior documented autoimmune or inflammatory disorders including but not limited
to the following:
--GI Disorders: (including inflammatory bowel disease [eg, ulcerative colitis, Crohn's
disease], diverticulitis (with the exception of a prior episode that has resolved), celiac
disease, or other serious gastrointestinal chronic conditions associated with diarrhea.
- 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 (eg, following Hashimoto syndrome) stable on hormone
replacement; or subjects with psoriasis not requiring systemic treatment..
- Because of compromised cellular immunity, patients who have a Known human
immunodeficiency virus (HIV), hepatitis C virus (HCV) or evidence of active hepatitis
B virus (HBV).
- Patients must not have 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.
- Individuals with a history of a different malignancy are ineligible except for the
following circumstances. Individuals with a history of other malignancies are eligible
if they have been disease-free for at least 5 years and are deemed by the investigator
to be at low risk for recurrence of that malignancy. Individuals with the following
cancers are eligible if diagnosed and treated within the past 5 years: non-invasive
cancer (such as, any in situ cancers) and basal cell or squamous cell carcinoma of the
skin.
- Prior allogeneic transplant
Step 2: Eligibility Criteria Prior to Randomization
Inclusion Criteria
- Patients must have obtained a complete remission with chemotherapy defined by the
absence of circulating blasts, and less than 5% blasts on bone marrow examination
following hematopoietic recovery
- Patient required no more than 2 cycles of chemotherapy or 4 cycles of a
hypomethylating agent (alone or in conjunction with venetoclax) to achieve remission.
- Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
- Laboratories:
Absolute Neutrophil Count >1,000/uL Platelets > 50,000/uL Bilirubin < 2.0 mg/dL Creatinine
<2.0 mg/dL AST/ALT < 3.0 x ULN
- For patients with evidence of minimal residual disease prior to vaccination, assessment
of minimal residual disease status by cytogenetics or FISH will be followed post
vaccination.
Exclusion Criteria
- 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 randomization
- Active or prior documented autoimmune or inflammatory disorders including but not
limited to the following:
- GI Disorders: (including inflammatory bowel disease [eg, ulcerative colitis,
Crohn's disease], diverticulitis (with the exception of a prior episode that has
resolved), celiac disease, or other serious gastrointestinal chronic conditions
associated with diarrhea.
- 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 (eg, following Hashimoto syndrome) stable on hormone
replacement; or subjects with psoriasis not requiring systemic treatment.
- Current or prior use of immunosuppressive medication within 14 days prior to first
dose of vaccine. 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), hepatitis C virus (HCV) or evidence of
active hepatitis B virus (HBV).
- History of hypersensitivity to durvalumab or any excipient
- Receipt of live attenuated vaccination within 30 days prior the first vaccine
- 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
vaccine, including dosing interruptions through 90 days after receipt of the last
vaccine. Refrain from egg cell donation during vaccination and for at least 90 days
after the last vaccine.
- 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
vaccine. Refrain from sperm donation during vaccination and for at least 90 days after
the last vaccine.
Step 3: Eligibility Criteria Prior to Treatment or Observation
- Resolution of all chemotherapy related grade III-IV toxicity as per CTC criteria 4.0
- Laboratories:
WBC > 2.0 X 103/uL Platelets > 50,000/uL Bilirubin < 2.0 mg/dL Creatinine <2.0 mg/dL
AST/ALT < 3.0 x ULN
- At least 2 doses of fusion vaccine were produced (Arm A only)
