Clinical Trials /

Dendritic Cell DKK1 Vaccine for Monoclonal Gammopathy and Stable or Smoldering Myeloma

NCT03591614

Description:

The purpose of this study is to study the safety and preliminary efficacy of a dendritic cell DKK1 vaccine against myeloma. Dendritic cells are immune cells that are collected from the blood of the patient at Case Western Reserve Medical Center and then brought into contact with DKK1, a molecule that is present of myeloma cells but not to a significant amount on other cells except for the prostate and the placenta. It is an investigational (experimental) vaccine that based on studies in the laboratory and in mice is expected to work by presentation of DKK1 to anticancer immune cells via dendritic cells leading to an immune attack on myeloma cells. It is experimental because it is not approved by the Food and Drug Administration (FDA).

Related Conditions:
  • Monoclonal Gammopathy of Undetermined Significance
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dendritic Cell DKK1 Vaccine for Monoclonal Gammopathy and Stable or Smoldering Myeloma
  • Official Title: A Pilot Study of Dendritic Cell DKK1 Vaccine for Patients With Monoclonal Gammopathy and Stable or Smoldering Myeloma

Clinical Trial IDs

  • ORG STUDY ID: CASE1A16
  • NCT ID: NCT03591614

Conditions

  • Monoclonal Gammopathy
  • Smoldering Myeloma
  • Myeloma

Interventions

DrugSynonymsArms
DKK1Dendritic cell DKK1 vaccine

Purpose

The purpose of this study is to study the safety and preliminary efficacy of a dendritic cell DKK1 vaccine against myeloma. Dendritic cells are immune cells that are collected from the blood of the patient at Case Western Reserve Medical Center and then brought into contact with DKK1, a molecule that is present of myeloma cells but not to a significant amount on other cells except for the prostate and the placenta. It is an investigational (experimental) vaccine that based on studies in the laboratory and in mice is expected to work by presentation of DKK1 to anticancer immune cells via dendritic cells leading to an immune attack on myeloma cells. It is experimental because it is not approved by the Food and Drug Administration (FDA).

Detailed Description

      The overall objective of this pilot study is to determine the safety and preliminary efficacy
      of a dendritic cell DKK1 vaccine in view of possible future use as a strategy to prevent
      progression of asymptomatic plasma cell disorders, maintain disease control, and ultimately
      contribute to eradication of multiple myeloma, light and heavy chain amyloidosis,
      immunoglobulin deposition disease, and other malignant and non-malignant diseases related to
      transformed plasma cells.

      Primary Objective Confirm the safety of dendritic cell DKK1 vaccine given every two weeks for
      three doses in patients with monoclonal gammopathy, stable or smoldering myeloma.

      Secondary Objectives

        1. Assess response according to international response criteria (> partial response, PR)
           and clinical benefit response (>minor response, MR, according to adapted EBMT criteria)

        2. Determine time to progression

        3. Describe progression-free and overall survival

      Correlative Objectives

        1. Explore correlation between myeloma DKK1 and PDL-1 expression and response

        2. Determine cellular immune response

        3. Assess serologic anti-DKK1 antibody response

      Study design including dose escalation / cohorts Pilot study with 3 patient safety run-in,
      possible dose level -1 (DL-1) if dose limiting toxicity occurs in one or more patients at the
      target dose level, and, at the first dose level where no dose limiting toxicity occurs,
      extension by 12 patients.

      DLT will be defined as any vaccine related toxicity > grade 3 that does not resolve to grade
      < 2 within 7 days. If any DLT occurs at DL-1 enrollment will be stopped and an amendment will
      be discussed.
    

Trial Arms

NameTypeDescriptionInterventions
Dendritic cell DKK1 vaccineExperimental5-10x106 DKK1 loaded dendritic cells. Three doses will be given two weeks apart, followed by 11 months of observations.
  • DKK1

Eligibility Criteria

        Inclusion Criteria:

          -  At any time prior to enrollment subjects must have IgG, IgA, kappa, or lambda
             monoclonal gammopathy confirmed in at least two assessments at least three months
             apart or histologically confirmed multiple myeloma or carry a diagnosis of smoldering
             myeloma based on prior documentation of serum m-spike (IgG or IgA) of at least 3g/dL
             serum m-spike (IgG or IgA) or 24h urine m-spike of at least 500mg/24h.

          -  Within 28 days prior to enrollment persistence of the clonal plasma cell disorder must
             be documented by presence of a clonal band on immunofixation of blood or urine or an
             abnormal serum free kappa/lambda ratio.

          -  Subjects with myeloma related organ dysfunction must have received prior therapy,
             reached at least partial remission with at least one of any number of prior regimens,
             and be candidates for observation off myeloma therapy based on lack of progression at
             least stable disease for at least 90 days prior to at study entry.

          -  Performance status ECOG performance status ≤ 2.

          -  Subjects must have laboratory test results within the following ranges:

               -  Hemoglobin ≥ 9.0 g/dl

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelet count ≥ 100,000/mcL

               -  Total bilirubin < 2.5 x institutional upper limit of normal

               -  AST (SGOT) ≤ 2.5 X institutional upper limit of normal

               -  ALT (SGPT) ≤ 2.5 X institutional upper limit of normal

               -  Calculated creatinine clearance (Cockcroft-Gault) ≥ 30ml/min

          -  Anti-myeloma treatment with proteasome inhibitors, IMiDsTM, corticosteroids, low dose
             cyclophosphamide (≤ 50mg per day) must have been discontinued at least 14 days prior
             to study entry. Conventional chemotherapy at conventional doses including
             cyclophosphamide at > 50mg per day must have been discontinued at least 28 days prior
             to study entry. At least 180 days must have passed since high dose chemotherapy used
             in the context of autologous stem cell transplantation. Prior radiation must have been
             completed at least 14 days prior to enrollment.

          -  Subjects must have the ability to understand and the willingness to sign a written
             informed consent document.

        Exclusion Criteria:

          -  Subjects receiving any other investigational agents.

          -  Concurrent use of any plasma cell directed therapy including corticosteroids (use of
             bisphosphonates is allowed).

          -  Subjects who have previously received an allogeneic stem cell transplant.

          -  Subjects with uncontrolled intercurrent illness including, but not limited to ongoing
             or active infection (including active HIV or hepatitis), symptomatic congestive heart
             failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
             situations that would limit compliance with study requirements.

          -  Women with childbearing potential (last menstrual period within less than 24 months
             unless hysterectomy or bilateral oophorectomy has been performed since) as well as
             pregnant women are excluded from this study because DKK1 is expressed in placental
             tissue and a DKK1 immune response could harm the child. Breastfeeding women are
             excluded from this study because antibodies made in response to the dendritic cell
             DKK1 vaccine could enter milk and affect the health of the breastfed child.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with dose limiting toxicity
Time Frame:Up to 1 year
Safety Issue:
Description:Toxicity will be assessed according to CTCAE v.4.03. Patients will have weekly CBC w. Differential, CMP, history, and physical. DLT will be defined as any vaccine related non-hematologic toxicity, neutropenia, anemia or thrombocytopenia > grade 3 that does not resolve to grade < 2 within 7 days.

Secondary Outcome Measures

Measure:Average time of progression-free survival
Time Frame:Up to 1 year
Safety Issue:
Description:Progression-free survival will be measured from administration of the first vaccine dose to progression as defined by updated uniform international response criteria or death of any cause, whichever comes first.
Measure:Average time of overall survival
Time Frame:Up to 1 year
Safety Issue:
Description:Overall survival will be measured from administration of the first vaccine dose to death from any cause.
Measure:Average time to progression
Time Frame:Up to 1 year
Safety Issue:
Description:Time to progression will be measured from administration of the first vaccine dose to progression as defined by updated uniform international response criteria
Measure:Best overall response
Time Frame:Up to 1 year
Safety Issue:
Description:Response will be evaluated according to updated uniform response criteria
Measure:Clinical Benefit Response
Time Frame:Up to 1 year
Safety Issue:
Description:Response will be evaluated according to updated uniform response criteria

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial Keywords

  • Vaccine
  • DKK1

Last Updated

November 18, 2019