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

NCT04634435 | Completed Phase 1 FDA Drug

• 1 other identifier: BHV1100-101
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicities following Combination Product administration

  90-100 days post Combination Product administration

• Incidence and severity of side effects related to the Combination Product

  90-100 days post Combination Product administration

Secondary Outcomes (13)

• 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

Study Arms (1)

BHV-1100 Combination Treatment

EXPERIMENTAL

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

Interventions

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

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

BHV-1100 Combination Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Biohaven Pharmaceuticals, Inc.: lead
• Dana-Farber Cancer Institute: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Hematologic Neoplasms

Interventions

Immunoglobulins, Intravenous; Interleukin-2

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Lymphokines; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: November 18, 2020
• Study Start: October 21, 2021
• Primary Completion: January 10, 2025
• Study Completion: January 10, 2025
• Last Updated: January 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)