Clinical trial NCT04634435: Autologous Memory-like NK Cell Therapy With BHV-1100 and Low Dose IL-2 in Multiple Myeloma Patients
Official title: A Phase 1 Study of Autologous Memory-like Natural Killer (NK) Cell Immunotherapy With BHV-1100 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2020-11-18
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Dose limiting toxicities following Combination Product administration
timeFrame: 90-100 days post Combination Product administration
measure: Incidence and severity of side effects related to the Combination Product
timeFrame: 90-100 days post Combination Product administration
Secondary outcomes:
measure: Rate of MRD (by ClonoSEQ®) conversion from positive to negative at 90-100 days after transplantation
timeFrame: 90-100 days post-ASCT
measure: Rate of MRD conversion from positive to negative
timeFrame: 1 year post-ASCT
measure: Rate of MRD conversion from positive to negative at any time during the maintenance phase
timeFrame: Start of maintenance therapy 90-100 days post ASCT until disease progression (approximately 2-3 years)
measure: Rate of PFS
timeFrame: 1 year post Combination Product administration
measure: Rate of OS
timeFrame: 1 year post Combination Product administration
measure: Best overall response rate per the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma
timeFrame: 90-100 days post-ASCT, 1 year post-ASCT, and overall during maintenance phase (approximately 3 years)
measure: Incidence and severity of cytokine release syndrome per ASBMT consensus grading
timeFrame: 100 days post Combination Product administration
measure: Incidence and severity of other Immune-related toxicities by CTCAE version 5.0
timeFrame: 100 days post Combination Product administration
measure: PK of BHV-1100 by determining plasma Tmax
timeFrame: 4 days post Combination Product administration
measure: PK of BHV-1100 by determining plasma Cmax
timeFrame: 4 days post Combination Product administration
measure: PK of BHV-1100 by determining plasma Cmin
timeFrame: 4 days post Combination Product administration
measure: PK of BHV-1100 by determining plasma AUC
timeFrame: 4 days post Combination Product administration
measure: PK of BHV-1100 by determining plasma t1/2
timeFrame: 4 days post Combination Product administration
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
References: