DC/AML Fusion Cell Vaccine vs DC/AML Fusion Cell Vaccine Plus Durvalumab vs Observation in Patients Who Achieve a Chemotherapy-induced Remission

• Status: Recruiting
• Trial end date: 0000-00-00
• Target enrollment: 105
• Participant gender: All

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)

• Durvalumab

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dana-Farber Cancer Institute
• Collaborator: Celgene
• Treatments: Antibodies, Monoclonal; Vaccines
• Last Updated: 2017-11-20

Criteria

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 and Durvalumab 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.

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

• 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 durvalumab or 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 dose of durvalumab or 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 dose of durvalumab or vaccine, including dosing interruptions through 90 days after receipt of the last dose of durvalumab. Refrain from egg cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab.

• Male subjects who are not employing an effective method of birth control from starting dose of durvalumab or vaccine, including dosing interruptions through 90 days after receipt of the last dose of durvalumab. Refrain from sperm cell donation while taking durvalumab and for at least 90 days after the last dose of durvalumab.

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 or B only)