Autologous Memory-like NK Cell Therapy With BHV-1100 and Low Dose IL-2 in Multiple Myeloma Patients

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