Autologous Memory-like NK Cell Therapy With BHV-1100 (Formerly KP1237), Low Dose IL-2 in Multiple Myeloma Patients

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04634435
• Other study ID #: BHV1100-101 (formerly KP001)
• Status: Recruiting
• Phase: Phase 1
• Start date: October 21, 2021
• Est. completion date: October 2026

Study information

• Verified date: August 2023
• Source: Biohaven Pharmaceuticals, Inc.
• Contact: Chief Medical Officer
• Phone: 203-404-0410
• Email: clinicaltrials[@]biohavenpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 cytokine induced memory-like (CIML) NK cells plus KP1237 and low dose IL-2 in newly diagnosed MM patients who have minimal residual disease (MRD+) in first remission prior to autologous stem cell transplant (ASCT).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: October 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 remission

• Achieve partial response or better with induction chemotherapy prior to ASCT according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma

• Be MRD+ disease 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 no evidence of active or decompensated heart failure, no recent history (past 6 months) acute myocardial infarction, no evidence of severe valvular disease and must have a LVEF over 50% at the time of transplant evaluation

• Adequate kidney function

• No evidence of moderate/severe restrictive or obstructive lung disease at the time of transplant evaluation

• Adequate bone marrow function

• Be willing to undergo CD34+ cell collection for stem cell transplant

• Be willing to undergo leukapherisis

• Adequate hepatic function

• If 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

Exclusion Criteria:

• Prior autologous or allogeneic hematopoietic stem cell transplant

• Prior cellular therapies, including NK cell therapy

• Prior treatment with monoclonal antibodies

• Prior treatment with melphalan

• Prior treatment with immunosuppressive or immunomodulatory agents within 30 days of enrollment

• Disease progression at the time of enrollment

• 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 or anti-myeloma drugs within 30 days of enrollment

• Patients with active clinically significant autoimmune diseases

• Patients with active, clinically significant cancer other than multiple myeloma

• Patients with neurological conditions that make difficult the assessment of neurologic toxicity of the Combination Product

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Combination Product:
• CIML NK Cells plus KP1237 and low dose IL-2
Single dose infusion of CIML NK Cells plus KP1237 followed by low dose IL-2

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Biohaven Pharmaceuticals, Inc.	Dana-Farber Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities following Combination Product dministration		100 days post Combination Product administration
Primary	Incidence and severity of side effects related to the Combination Product		100 days post Combination Product administration
Secondary	Rate of MRD conversion from positive to negative		90-100 days post-ASCT
Secondary	Rate of MRD conversion from positive to negative		1 year post-ASCT
Secondary	Rate of MRD conversion from positive to negative during the maintenance phase		Start of maintenance therapy 90-100 days post ASCT until disease progression (approximately 2-3 years)
Secondary	Rate of PFS		1 year post Combination Product administration
Secondary	Rate of OS		1 years post Combination Product administration
Secondary	Best overall response rate per the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma		90-100 days post-ASCT, 1 year post-ASCT, and overall during maintenance phase (approximately 3 years)
Secondary	Incidence and severity of cytokine release syndrome per ASBMT consensus grading		100 days post Combination Product administration
Secondary	Incidence and severity of other Immune-related toxicities by CTCAE version 5.0		100 days post Combination Product administration
Secondary	PK of the KP1237 by determining plasma Cmax		4 days post Combination Product administration
Secondary	PK of the KP1237 by determining plasma Cmin		4 days post Combination Product administration
Secondary	PK of the KP1237 by determining plasma AUC		4 days post Combination Product administration
Secondary	PK of the KP1237 by determining plasma t1/2		4 days post Combination Product administration