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).
Title
- Brief Title: Autologous Memory-like NK Cell Therapy With BHV-1100 (Formerly 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:
BHV1100-101 (formerly KP001)
- NCT ID:
NCT04634435
Conditions
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
Name | Type | Description | Interventions |
---|
Newly diagnosed multiple myeloma patients | Experimental | Newly 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: | Biohaven Pharmaceuticals, Inc. |
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
August 11, 2021