autologous memory-like nk cell therapy with bhv-1100 and low dose il-2 in multiple myeloma patients

Conditions: Multiple Myeloma

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.


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 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

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