NCT04634435已完成1 期
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
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 2
- 主要终点
- Dose limiting toxicities following Combination Product administration
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Dose limiting toxicities following Combination Product administration
时间窗: 90-100 days post Combination Product administration
Incidence and severity of side effects related to the Combination Product
时间窗: 90-100 days post Combination Product administration
次要结局
- 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)
- 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))
- Incidence and severity of cytokine release syndrome per ASBMT consensus grading(100 days post Combination Product administration)
- Incidence and severity of other Immune-related toxicities by CTCAE version 5.0(100 days post Combination Product administration)
- PK of BHV-1100 by determining plasma Tmax(4 days post Combination Product administration)
- PK of BHV-1100 by determining plasma Cmax(4 days post Combination Product administration)
- PK of BHV-1100 by determining plasma Cmin(4 days post Combination Product administration)
- PK of BHV-1100 by determining plasma AUC(4 days post Combination Product administration)
- PK of BHV-1100 by determining plasma t1/2(4 days post Combination Product administration)
研究者
研究点 (2)
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