Autologous Memory-like NK Cell Therapy With BHV-1100 and Low Dose IL-2 in Multiple Myeloma Patients
Phase 1
Completed
- Conditions
- Multiple Myeloma
- Interventions
- Combination Product: CIML NK Cells plus KP1237 and low dose IL-2
- Registration Number
- NCT04634435
- Lead Sponsor
- Biohaven Pharmaceuticals, Inc.
- Brief Summary
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 BHV-1100 plus cytokine induced memory-like (CIML) NK cells plus IVIG and low dose IL-2 in the peri-transplant setting in MM patients with minimal residual disease (MRD+) in first or second remission.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 7
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 or second remission
- Achieve partial response or better with induction chemotherapy prior to ASCT according to the IMWG Uniform Response Criteria for Multiple Myeloma
- Be MRD+ 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 a creatinine clearance > 45 mL/min/m2 at the time of transplant evaluation
- If frozen stem cells from earlier mobilized leukapheresis are unavailable at the time of mobilized leukapheresis, patients must meet parameters/criteria according to institutional SOP for autologous stem cell apheresis
- Be willing and clinically stable to undergo stem-cell mobilized and collect enough CD34+ cells sufficient for 2 ASCT per institutional guidelines or investigator discretion or have sufficient frozen cells from a SoC collection prior to signing study consent
- Be willing and clinically stable to undergo a non-mobilized MNC-Apheresis while admitted to the hospital to generate CIML NK cells
- Be willing to undergo maintenance after ASCT per NCCN guidelines based on disease risk
- If a woman 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
- Patients must meet adequate organ function/reserve based on institutional SOP for autologous stem cell transplant eligibility
- Non-secretory MM can participate if they have measurable disease in the bone marrow and are amenable to be followed by MRD testing
Exclusion Criteria
- Prior autologous or allogeneic hematopoietic stem cell transplant
- Prior cellular therapies, including NK cell therapy
- Prior treatment with monoclonal antibodies, within 28 days of MCN apheresis
- Prior treatment with high dose melphalan
- Prior treatment with immunosuppressive or immunomodulatory agents with exception of 5 mg or less of prednisone daily, within 14 days of MCN-Apheresis
- Disease progression at the time of study treatment
- 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 therapy
- Patients with active, clinically significant autoimmune diseases
- Patients with active, clinically significant cancer other than multiple myeloma
- Patients with severe, uncontrolled psychiatric or neurological conditions that make difficult the assessment of neurologic toxicity of the study treatment
- Patients who have received anti-MM therapy (with the exclusion of monoclonal antibodies) within 14 days of study treatment
- More than two prior lines of anti-myeloma therapy, with induction therapy followed by maintenance being considered as one line and CyBorD to RVD transition in the absence of progressive disease being considered as one line
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Newly diagnosed multiple myeloma patients CIML NK Cells plus KP1237 and low dose IL-2 Newly diagnosed MM patients who have minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT)
- Primary Outcome Measures
Name Time Method Incidence and severity of side effects related to the Combination Product 90-100 days post Combination Product administration Dose limiting toxicities following Combination Product administration 90-100 days post Combination Product administration
- Secondary Outcome Measures
Name Time Method Rate of MRD (by ClonoSEQ®) conversion from positive to negative at 90-100 days after transplantation 90-100 days post-ASCT Rate of MRD conversion from positive to negative 1 year post-ASCT Rate of MRD conversion from positive to negative at any time during the maintenance phase Start of maintenance therapy 90-100 days post ASCT until disease progression (approximately 2-3 years) Rate of PFS 1 year post Combination Product administration Rate of OS 1 year post Combination Product administration Best overall response rate per the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma 90-100 days post-ASCT, 1 year post-ASCT, and overall during maintenance phase (approximately 3 years) Incidence and severity of cytokine release syndrome per ASBMT consensus grading 100 days post Combination Product administration Incidence and severity of other Immune-related toxicities by CTCAE version 5.0 100 days post Combination Product administration PK of BHV-1100 by determining plasma Tmax 4 days post Combination Product administration PK of BHV-1100 by determining plasma Cmax 4 days post Combination Product administration PK of BHV-1100 by determining plasma Cmin 4 days post Combination Product administration PK of BHV-1100 by determining plasma AUC 4 days post Combination Product administration PK of BHV-1100 by determining plasma t1/2 4 days post Combination Product administration
Trial Locations
- Locations (1)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States