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

NCT ID: NCT04634435

Last Updated: 2025-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-21
• Study Completion Date: 2025-01-10

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.

Conditions

Multiple Myeloma

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

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BHV-1100 Combination Treatment

Group Type: EXPERIMENTAL

BHV-1100 plus cytokine induced memory-like (CIML) NK cells plus IVIG and low dose IL-2

Intervention Type: COMBINATION_PRODUCT

Single dose infusion of BHV-1100 plus CIML NK Cells plus IVIG, followed by low dose IL-2

Interventions

BHV-1100 plus cytokine induced memory-like (CIML) NK cells plus IVIG and low dose IL-2

Single dose infusion of BHV-1100 plus CIML NK Cells plus IVIG, followed by low dose IL-2

Intervention Type: COMBINATION_PRODUCT

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dana-Farber Cancer Institute

OTHER

Sponsor Role: collaborator

Biohaven Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

BHV1100-101

Identifier Type: -

Identifier Source: org_study_id