Clinical Trials /

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

NCT03059485

Description:

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)

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: DC/AML Fusion Cell Vaccine vs DC/AML Fusion Cell Vaccine Plus Durvalumab vs Observation in Patients Who Achieve a Chemotherapy-induced Remission
  • Official Title: A Randomized Phase II Clinical Trial of Dendritic Cell/AML Fusion Cell Vaccine Versus DC/AML Fusion Cell Vaccine in Conjunction With Durvalumab, Versus Observation in Patients Who Achieve a Chemotherapy-induced Remission

Clinical Trial IDs

  • ORG STUDY ID: 16-593
  • NCT ID: NCT03059485

Conditions

  • Acute Myelogenous Leukemia

Interventions

DrugSynonymsArms
DurvalumabMEDI-4736DC/AML Vaccine + Durvalumab
DC/AML Fusion VaccineDC/AML Vaccine

Purpose

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

Detailed Description

      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 and in combination
      with Durvalumab. 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.

      Durvalumab is a check point inhibitor which is being combined here to further amplify the
      immune activity of the vaccine. It is a monoclonal antibody, which is known to take the
      brakes off the immune system to restore immunity. In this study, the investigators will add
      Durvalumab in combination with the vaccine with the hope of improving immunity even further.
    

Trial Arms

NameTypeDescriptionInterventions
DC/AML VaccineExperimental- Patients will be vaccinated with DC/AML Fusion Vaccine
    DC/AML Vaccine + DurvalumabExperimentalPatients will be vaccinated with DC/AML Fusion Vaccine Patients will receive 3 doses of Durvalumab given at 28 day intervals Durvalumab, will be delivered intravenously
    • Durvalumab
    ObservationExperimental- Patients will be monitored with routine labs and bone marrow biopsies

      Eligibility 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)
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:All
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Progression Free Survival
      Time Frame:2 years
      Safety Issue:
      Description:

      Secondary Outcome Measures

      Measure:Overall Survival
      Time Frame:2 years
      Safety Issue:
      Description:
      Measure:Assessing Toxicity using CTCAE version 4.03
      Time Frame:2 years
      Safety Issue:
      Description:

      Details

      Phase:Phase 2
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:Dana-Farber Cancer Institute

      Trial Keywords

      • Leukemia

      Last Updated

      February 16, 2017