A Phase 1 Study of Autologous Memory-like Natural Killer (NK) Cell Immunotherapy with BHV-1100 (formerly KP1237) and IVIG followed by low dose IL-2 as Early Post-Autologous Transplant Consolidation in Minimal Residual Disease Positive, Multiple Myeloma (MM) Patients in First or Second Remission
Trial 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 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.
Eligibility Requirements
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