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
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 1
- 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
研究组 & 干预措施
BHV-1100 Combination Treatment
Experimental
干预措施: BHV-1100 plus cytokine induced memory-like (CIML) NK cells plus IVIG and low dose IL-2 (Combination Product)
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 OS(1 year post Combination Product administration)
- 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 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 PFS(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 (1)
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