Open-Label, Multicenter, Phase 1 Study to Assess the Safety of P BCMA-101 in Subjects With Relapsed / Refractory Multiple Myeloma (MM) Followed by a Phase 2 Assessment of Response and Safety (PRIME)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 105
- 试验地点
- 16
- 主要终点
- Phase 1: Assess the Safety of P-BCMA-101
研究概览
简要总结
Phase 1 of the study is comprised of an open-label, single ascending dose (SAD), multiple cohort study; a multiple dose cycle administration cohort study; and a combination administration study of P-BCMA-101 autologous T stem cell memory (Tscm) CAR-T cells in patients with relapsed / refractory MM. Followed by a Phase 2, open-label, efficacy and safety study. Rimiducid may be administered as indicated.
详细描述
Phase 1 follows a 3 + 3 design of dose-escalating cohorts. Phase 2 of the study is an open-label multi-center efficacy and safety study. After a patient enrolls, leukapheresis will be performed to obtain peripheral blood mononuclear cells which will be sent to a manufacturing site to produce P-BCMA-101 CAR-T cells. The cells will then be returned to the investigational site and, after a standard chemotherapy based conditioning regimen, will be administered to the patient across 1-3 infusions, with or without combination therapy. Treated patients will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, ≥18 years of age
- •Must have a confirmed diagnosis of active MM
- •Must have measurable MM
- •Must have relapsed / refractory MM, having received treatment with proteasome inhibitor and IMiD [Phase 2: Must have relapsed / refractory MM, and refractory to last line of therapy, having received treatment with proteasome inhibitor, an IMiD, CD38 targeted therapy and undergone autologous stem cell transplant (ASCT) or not a candidate for ASCT.]
- •Must have adequate hepatic, renal, cardiac and hematopoietic function
排除标准
- •Is pregnant or lactating
- •Has inadequate venous access and/or contraindications to leukapheresis
- •Has active hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, amyloidosis, significant autoimmune, CNS or other malignant disease
- •Has an active second malignancy (not disease-free for at least 5 years) in addition to MM, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma.
- •Has active autoimmune disease
- •Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy, etc.
- •Has an active systemic infection
- •Has hepatitis B or C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome.
- •Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol
- •Has receiving immunosuppressive or other contraindicated therapies within the excluded time frame from entry
- •Has CNS metastases or symptomatic CNS involvement
- •Has a history of having undergone allogeneic stem cell transplantation, or any other allogeneic or xenogeneic transplant, or has undergone autologous transplantation within 90 days.
- •Unable to take acetylsalicylic acid (ASA) daily as prophylactic anticoagulation. (Cohorts R and RP only).
- •History of thromboembolic disease within the past 6 months, regardless of anticoagulation (Cohorts R and RP only).
研究组 & 干预措施
Phase 1 P-BCMA-101 CAR-T cells (Cohort A)
Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
Phase 1: P-BCMA-101 CAR-T cells
Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 1: P-BCMA-101 CAR-T cells
Single ascending dose cohorts, given in a single intravenous infusion of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
Phase 1 P-BCMA-101 CAR-T cells (Cohort A)
Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 1 P-BCMA-101 CAR-T cells (Cohort B)
Single dose given across three intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 1 P-BCMA-101 CAR-T cells (Cohort B)
Single dose given across three intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
Phase 1 P-BCMA-101 CAR-T cells (Cohort C)
Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 1 P-BCMA-101 CAR-T cells (Cohort C)
Single dose given across two intravenous infusions of CAR-T cells. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R)
Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort R)
Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP)
Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before apheresis. Rimiducid may be administered as indicated.
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RP)
Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before apheresis. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT)
Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 1 P-BCMA-101 CAR-T cells with Comb.Therapy (Cohort RIT)
Single intravenous infusion of CAR-T cells, with combination therapy, beginning one week before CAR-T infusion. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
Phase 2: P-BCMA-101 CAR-T Cells
CAR-T cells administered via intravenous infusion as a total dose
干预措施: P-BCMA-101 CAR-T cells (Biological)
Phase 2: P-BCMA-101 CAR-T Cells
CAR-T cells administered via intravenous infusion as a total dose
干预措施: Rimiducid (Drug)
结局指标
主要结局
Phase 1: Assess the Safety of P-BCMA-101
时间窗: Baseline through Day 28
Incidence and severity of treatment-emergent adverse events
Phase 1: Maximum Tolerated Dose of P-BCMA-101
时间窗: Baseline through Day 28
Rate of dose limiting toxicities (DLT)
Phase 2: Assess the Safety of P-BCMA-101
时间窗: Baseline through 24 months
Incidence and severity of treatment-emergent adverse events
Phase 2: Assess the Efficacy of P-BCMA-101 (ORR)
时间窗: Baseline through 24 months
According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Overall Response Rate (ORR)-Percentage of patients with complete response (CR), very good partial response (VGPR), or partial response (PR).
Phase 2: Assess the Efficacy of P-BCMA-101 (DOR)
时间窗: Baseline through 24 months
According to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma: Duration of Response (DOR)-Time from complete response (CR), very good partial response (VGPR), or partial response (PR) to progressive disease.
次要结局
- Phase 1:Assess the Feasibility P-BCMA-101(Baseline through Month 24)
- Phase 1: Anti-myeloma Effect of P-BCMA-101 (ORR)(Baseline through Month 24)
- Phase 1:Assess the Safety of P-BCMA-101(Baseline through Month 24)
- Phase 1: Anti-myeloma Effect of P-BCMA-101 (TTR)(Baseline through Month 24)
- Phase 1: Anti-myeloma Effect of P-BCMA-101 (DOR)(Baseline through Month 24)
- Phase 1: Anti-myeloma Effect of P-BCMA-101 (PFS)(Baseline through Month 24)
- Phase 1: Anti-myeloma Effect of P-BCMA-101 (OS)(Baseline through Month 24)
- Phase 1: The Effect of Cell Dose to Guide Selection of Doses for Further Assessment in Phase 2/3 Studies(Baseline through Month 24)
- Phase 2: Incidence and Severity of Cytokine Release Syndrome (CRS)(Baseline through Month 24)
- Phase 2: Evaluate Efficacy Endpoints (IL-6)(Baseline through Month 24)
- Phase 2: Evaluate Efficacy Endpoints (C)(Baseline through Month 24)
- Phase 2: Evaluate Efficacy Endpoints (OS)(Baseline through Month 24)
- Phase 2: Evaluate Efficacy Endpoints (PFS)(Baseline through Month 24)
- Phase 2: Evaluate Efficacy Endpoints (R)(Baseline through Month 24)
- Phase 2: Evaluate Efficacy Endpoints (TTR)(Baseline through Month 24)
- Phase 2: Evaluate Efficacy Endpoints (MRD)(Baseline through Month 24)