Clinical Trials /

Phase 1 Study of Autologous Memory-like NK Cell Therapy With KP1237, Low Dose IL-2 in Multiple Myeloma Patients

NCT04634435

Description:

This is an open-label single center Phase 1a/1b study with the primary objective of establishing the safety and exploring the efficacy of infusing the ex vivo combination product of cytokine induced memory-like (CIML) NK cells plus KP1237 and low dose IL-2 in newly diagnosed MM patients who have minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT).

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of Autologous Memory-like NK Cell Therapy With KP1237, Low Dose IL-2 in Multiple Myeloma Patients
  • Official Title: Phase 1 Study of Autologous Memory-like NK Cell Immunotherapy in Combination With KP1237 and Low Dose IL-2 as Early Post Autologous Transplant Consolidation in Minimal Residual Disease Positive, Newly Diagnosed Multiple Myeloma Patients

Clinical Trial IDs

  • ORG STUDY ID: KP-001
  • NCT ID: NCT04634435

Conditions

  • Multiple Myeloma

Purpose

This is an open-label single center Phase 1a/1b study with the primary objective of establishing the safety and exploring the efficacy of infusing the ex vivo combination product of cytokine induced memory-like (CIML) NK cells plus KP1237 and low dose IL-2 in newly diagnosed MM patients who have minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT).

Trial Arms

NameTypeDescriptionInterventions
Newly diagnosed multiple myeloma patientsExperimentalNewly diagnosed MM patients who have minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT)

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Had measurable disease according to Standard Diagnostic Criteria at the time of
                 initial Multiple Myeloma diagnosis
    
              -  Meets criteria for symptomatic multiple myeloma at the time of induction chemotherapy
    
              -  Is transplant eligible based on clinician judgement
    
              -  Willing to undergo ASCT in first remission
    
              -  Achieve partial response or better with induction chemotherapy prior to ASCT according
                 to the International Myeloma Working Group (IMWG) Uniform Response Criteria for
                 Multiple Myeloma
    
              -  Be MRD+ disease upon restaging prior to stem cell collection and ASCT
    
              -  Eastern Cooperative Oncology Group (EGOG) performance status score of less than 2
    
              -  Life expectancy greater than six months
    
              -  Have no evidence of active or decompensated heart failure, no recent history (past 6
                 months) acute myocardial infarction, no evidence of severe valvular disease and must
                 have a LVEF over 50% at the time of transplant evaluation
    
              -  Adequate kidney function
    
              -  No evidence of moderate/severe restrictive or obstructive lung disease at the time of
                 transplant evaluation
    
              -  Adequate bone marrow function
    
              -  Be willing to undergo CD34+ cell collection for stem cell transplant
    
              -  Be willing to undergo leukapherisis
    
              -  Adequate hepatic function
    
              -  If of child-bearing potential, be willing to follow birth control and pregnancy
                 testing practice as recommended
    
              -  Be willing to undergo bone marrow aspirate and biopsy as per treatment plan
    
            Exclusion Criteria:
    
              -  Prior autologous or allogeneic hematopoietic stem cell transplant
    
              -  Prior cellular therapies, including NK cell therapy
    
              -  Prior treatment with monoclonal antibodies
    
              -  Prior treatment with melphalan
    
              -  Prior treatment with immunosuppressive or immunomodulatory agents within 30 days of
                 enrollment
    
              -  Disease progression at the time of enrollment
    
              -  Non secretory multiple myeloma (defined as normal serum and urine immunofixation and
                 normal serum free light chain assay)
    
              -  History of plasma cell leukemia at any time prior to enrollment
    
              -  Patients seropositive for the human immunodeficiency virus (HIV)
    
              -  Uncontrolled, Hepatitis C Virus or Hepatitis B Virus infection
    
              -  Patient receiving other investigational or anti-myeloma drugs within 30 days of
                 enrollment
    
              -  Patients with active clinically significant autoimmune diseases
    
              -  Patients with active, clinically significant cancer other than multiple myeloma
    
              -  Patients with neurological conditions that make difficult the assessment of neurologic
                 toxicity of the Combination Product
          
    Maximum Eligible Age:75 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Dose limiting toxicities following Combination Product dministration
    Time Frame:100 days post Combination Product administration
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Rate of MRD conversion from positive to negative
    Time Frame:90-100 days post-ASCT
    Safety Issue:
    Description:
    Measure:Rate of MRD conversion from positive to negative
    Time Frame:1 year post-ASCT
    Safety Issue:
    Description:
    Measure:Rate of MRD conversion from positive to negative during the maintenance phase
    Time Frame:Start of maintenance therapy 90-100 days post ASCT until disease progression (approximately 2-3 years)
    Safety Issue:
    Description:
    Measure:Rate of PFS
    Time Frame:1 year post Combination Product administration
    Safety Issue:
    Description:
    Measure:Rate of OS
    Time Frame:1 years post Combination Product administration
    Safety Issue:
    Description:
    Measure:Best overall response rate per the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma
    Time Frame:90-100 days post-ASCT, 1 year post-ASCT, and overall during maintenance phase (approximately 3 years)
    Safety Issue:
    Description:
    Measure:Incidence and severity of cytokine release syndrome per ASBMT consensus grading
    Time Frame:100 days post Combination Product administration
    Safety Issue:
    Description:
    Measure:Incidence and severity of other Immune-related toxicities by CTCAE version 5.0
    Time Frame:100 days post Combination Product administration
    Safety Issue:
    Description:
    Measure:PK of the KP1237 by determining plasma Cmax
    Time Frame:4 days post Combination Product administration
    Safety Issue:
    Description:
    Measure:PK of the KP1237 by determining plasma Cmin
    Time Frame:4 days post Combination Product administration
    Safety Issue:
    Description:
    Measure:PK of the KP1237 by determining plasma AUC
    Time Frame:4 days post Combination Product administration
    Safety Issue:
    Description:
    Measure:PK of the KP1237 by determining plasma t1/2
    Time Frame:4 days post Combination Product administration
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Kleo Pharmaceuticals

    Trial Keywords

    • Cell Therapy
    • CIML NK cell therapy
    • cytokine induced memory-like natural killer cell therapy
    • immunotherapy
    • antibody-dependent cell-mediated cytotoxicity
    • ADCC
    • CD38 positive
    • CD38+
    • plasma cells
    • multiple myeloma
    • hematological malignancies

    Last Updated

    November 18, 2020