Clinical Trials /

Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma

NCT03782064

Description:

This research study is studying a cancer vaccine called Dendritic Cell/MM Fusion vaccine (DC/MM vaccine) in combination with nivolumab, as a possible treatment for multiple myeloma (MM). The drugs involved in this study are: - Dendritic Cell/MM Fusion vaccine (DC/MM vaccine) - Nivolumab, an immunotherapy drug

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma
  • Official Title: A Phase II Trial of Vaccination With Dendritic Cell (DC)/Myeloma Fusions in Combination With Nivolumab in Patients With Relapsed Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 18-280
  • NCT ID: NCT03782064

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
NivolumabNivolumab+DC/myeloma fusions/GM-CSF
DC/myeloma fusions/GM-CSFNivolumab+DC/myeloma fusions/GM-CSF

Purpose

This research study is studying a cancer vaccine called Dendritic Cell/MM Fusion vaccine (DC/MM vaccine) in combination with nivolumab, as a possible treatment for multiple myeloma (MM). The drugs involved in this study are: - Dendritic Cell/MM Fusion vaccine (DC/MM vaccine) - Nivolumab, an immunotherapy drug

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved the DC/MM vaccine as a
      treatment for any disease.

      The FDA has not approved nivolumab for multiple myeloma. A similar immunotherapy drug used in
      combination with IMiDs (drugs that regulate or modify the immune system) was associated with
      higher risk of death in another research trial in patients with multiple myeloma; however,
      nivolumab has been approved for use in several other types of cancers.

      The FDA has not approved the combination of nivolumab with the DC/MM vaccine as a treatment
      for any disease.

      In this research study, the investigators wish to determine whether nivolumab administered in
      combination with the DC/MM vaccine will help promote an immune response against multiple
      myeloma cells.

      An immune response is any reaction by the immune system. It helps the body distinguish itself
      from substances foreign to it, such as infections and dangerous substances. Cancer cells have
      unique markers that distinguish them from normal cells, which can potentially serve as
      targets for the immune system.

      The DC/MM vaccine is an investigational agent that tries to help the immune system recognize
      and fight against cancer cells, utilizing those unique markers. 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 suggest that when dendritic
      cells (a type of immune cell that helps to tell your immune system what is good and what is
      bad) and tumor cells are brought together, the dendritic cells can stimulate immune responses
      against the tumor.

      Nivolumab is a monoclonal antibody. Antibodies are part of your immune system; they are a
      type of protein that protects the body against foreign invaders, called antigens, by grabbing
      hold of antigens to stop them from invading your system. Monoclonal indicated that this
      antibody was made in a lab. Nivolumab has been shown to react against cancer cells, including
      MM cells. The investigators hope that the addition of nivolumab with the DC/MM vaccine will
      help the body fight MM
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab+DC/myeloma fusions/GM-CSFExperimentalNivolumab will be given every two weeks The DC/myeloma fusion vaccine/GM-CSF is administered 4 days per cycle
  • Nivolumab
  • DC/myeloma fusions/GM-CSF

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have Patients with relapsed multiple myeloma with prior treatment of an
             IMID and proteasome inhibitor.

          -  Age ≥18 years.

          -  ECOG performance status ≤2

          -  Patients must have > 20% plasma cells in the bone marrow aspirate differential <30
             days prior to enrollment.

          -  ANC > 1000; Platelets > 75K without transfusional support

          -  Participants must have normal organ function as defined below:

               -  total bilirubin ≤1.5 × institutional upper limit of normal

               -  AST(SGOT)/ALT(SGPT) ≤3 × institutional upper limit of normal

               -  creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

          -  The effects of DC/MM fusion and nivolumab 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 she or her partner is participating in this study, she
             should inform her treating physician immediately. Men treated or enrolled on this
             protocol must also agree to use adequate contraception prior to the study, for the
             duration of study participation, and 5 months after completion of treatment.

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

        -Participants who are receiving any other investigational agents.

        3.2.2 Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in
        serum as measured by electrophoresis and immunofixation and the absence of Bence-Jones
        protein in the urine defined by use of conventional electrophoresis and immunofixation
        techniques and the absence of involved serum free light chain >100 mg/L]. Patients with
        light chain MM detected in the serum by free light chain assay are eligible.

          -  Patients with Plasma Cell Leukemia

          -  Because of compromised cellular immunity, patients who have a known human
             immunodeficiency virus (HIV), active hepatitis C virus (HCV) or active hepatitis B
             virus (HBV).

          -  Myocardial infarction within 6 months prior to enrollment or New York Heart
             Association (NYHA) Class III or IV heart failure (see Appendix H), uncontrolled
             angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
             of acute ischemia or active conduction system abnormalities. Prior to study entry, any
             ECG abnormality at screening will be documented by the investigator as not medically
             relevant.

          -  Active or prior documented autoimmune or inflammatory disorders including but not
             limited to the following:

               -  GI Disorders: (including inflammatory bowel disease [e.g. 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 (e.g. following Hashimoto syndrome) stable on hormone
             replacement; or subjects with psoriasis not requiring systemic treatment.

          -  Individuals with a history of a different malignancy are ineligible except for the
             following circumstances. Note: 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.

          -  Female patients who are pregnant (positive β-HCG) or breastfeeding

          -  Prior organ transplant requiring immunosuppressive therapy.

          -  Patients who previously received PD-1 antibody and have experienced toxicities
             resulting in treatment discontinuation.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients who develop immunologic response to nivolumab and the DC/MM fusion vaccine
Time Frame:2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of patients who achieve a clinical response (SD, PR, VGPR, CR)
Time Frame:2 years
Safety Issue:
Description:
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:2 years
Safety Issue:
Description:
Measure:Number of patients who are alive without progression at 2 years
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Multiple Myeloma

Last Updated

May 30, 2019