Open-Label, Multicenter, Phase 1 Study to Assess the Safety of P-BCMA-ALLO1 in Subjects With Relapsed / Refractory Multiple Myeloma (MM)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 275
- 试验地点
- 31
- 主要终点
- Phase 1 Part 1: Assess the safety and maximum tolerated dose (MTD) of P-BCMA-ALLO1 based on dose limiting toxicities (DLT)
研究概览
简要总结
Phase 1 study comprised of open-label, dose escalation, multiple cohorts of P-BCMA-ALLO1 allogeneic T stem cell memory (Tscm) CAR-T cells in subjects with relapsed / refractory Multiple Myeloma (RRMM).
详细描述
Phase 1/1b study: Phase 1 Part 1 is a weight-based dose escalation following a 3+3 design of dose-escalating cohorts. Phase 1 Part 2 includes administration at fixed doses. After enrollment, subjects may receive a lymphodepletion therapy regimen before administration of allogeneic CAR-T cells, administered as a single or multiple dose(s). Treated subjects will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated. Phase 1b of the study will undergo further expansion of cohorts/arms from Phase 1 Parts 1 or 2 or an intermediate dose between cohort levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Must have signed written, informed consent.
- •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 a proteasome inhibitor, immunomodulatory agent (IMiD), and anti-CD38 therapy.
- •Must be willing to practice birth control from the time of Screening and throughout the first year of the study after P-BCMA-ALLO1 administration.
- •Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 3 days prior to initiating the lymphodepletion therapy regimen (females of childbearing potential).
- •Must be at least 90 days since autologous stem cell transplant, if performed.
- •Must have adequate vital organ function within pre-determined parameters.
- •Must have recovered from toxicities due to prior therapies.
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
排除标准
- •Is pregnant or lactating.
- •Has inadequate venous access.
- •Has active hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, or amyloidosis.
- •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 a history of hepatitis B, hepatitis C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome. Subjects with a history of treated hepatitis C can be enrolled if negative by Hepatitis C PCR on multiple occasions.
- •Is positive for cytomegalovirus (CMV) by PCR, CMV immunoglobulin M (IgM) antibody, or Coronavirus disease 2019 (COVID-19) by PCR.
- •Has New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of myocardial infarction or significant arrhythmia.
- •Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol.
- •Has received prior allogeneic cellular therapy or gene therapy.
- •Has received anti-cancer medications within 2 weeks of the time of initiating conditioning LD therapy.
- •Has received monoclonal antibody therapy within 4 weeks of initiating conditioning LD therapy.
- •Has received immunosuppressive medications within 2 weeks of the time of administration of P-BCMA-ALLO1, and/or expected to require them while on study.
- •Has received systemic corticosteroid therapy within 1 week or 5 half-lives (whichever is shorter) of the administration of P-BCMA-ALLO1 or is expected to require it during the course of the study.
- •Has CNS metastases or symptomatic CNS involvement of their myeloma.
- •Has a history of severe immediate hypersensitivity reaction to any of the agents used in this study.
- •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.
- •Arms R, RS, RP1, RP1.5 and RP2 Only: a) Has received a live vaccine within the last 28 days of the first administration of agents used in Arm R or RS, b) Has any known hypersensitivity or severe reactions or toxicity to agents used in Arms R or RS.
- •Has received radiation within 1 week of initiating conditioning LD therapy.
- •Administration of a live vaccine within the last 28 days prior to administration of LD therapy.
研究组 & 干预措施
P-BCMA-ALLO1 CAR-T cells (Arm RP1)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm CP1)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm CP1.5)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1.5.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm S)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm F)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen F.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm N)
Single weight-based IV administration of P-BCMA-ALLO1. Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm P1)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm160)
Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm P1.5)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1.5.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm RP1.5)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1.5.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm P2)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P2.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm R)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen R.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm S)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm F)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen F.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm N)
Single weight-based IV administration of P-BCMA-ALLO1. Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm P1)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm P2)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P2.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm R)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen R.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm RS)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RS.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm RS)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RS.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm C)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen C.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm C)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen C.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm160)
Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm480)
Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm480)
Single fixed dose IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen S, P1, P1.5 or P2.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm P1.5)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen P1.5.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm RP1)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm RP1.5)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP1.5.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm RP2)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP2.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm RP2)
Single weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen RP2.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm CP1)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm CP1.5)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP1.5.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm CP2)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP2.
Rimiducid may be administered as indicated.
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm CP2)
Cyclic weight-based IV administration of P-BCMA-ALLO1 following conditioning chemotherapy regimen CP2.
Rimiducid may be administered as indicated.
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm MP1.5)
Single weight based IV administration of P-BCMA-ALLO1 and methotrexate following conditioning chemotherapy regimen MP1.5 Rimiducid may be administered as indicated
干预措施: P-BCMA-ALLO1 CAR-T cells (Biological)
P-BCMA-ALLO1 CAR-T cells (Arm MP1.5)
Single weight based IV administration of P-BCMA-ALLO1 and methotrexate following conditioning chemotherapy regimen MP1.5 Rimiducid may be administered as indicated
干预措施: Rimiducid (Drug)
P-BCMA-ALLO1 CAR-T cells (Arm MP1.5)
Single weight based IV administration of P-BCMA-ALLO1 and methotrexate following conditioning chemotherapy regimen MP1.5 Rimiducid may be administered as indicated
干预措施: Methotrexate (Drug)
结局指标
主要结局
Phase 1 Part 1: Assess the safety and maximum tolerated dose (MTD) of P-BCMA-ALLO1 based on dose limiting toxicities (DLT)
时间窗: Baseline through Day 28
Rate of dose limiting toxicities (DLT)
Phase 1 Part 1: Assess the safety and maximum tolerated dose (MTD) of P-BCMA-ALLO1 based on dose limiting toxicities (DLT)
时间窗: Baseline through Day 28
Rate of dose limiting toxicities (DLT)
Phase 1 Part 2: Assess the safety and tolerability of P-BCMA-ALLO1 when administered as a fixed dose of cells.
时间窗: Baseline through 36 months
Frequency and severity of adverse events, including cytokine release syndrome.
Phase 1b: The effect of cell dose and study arm
时间窗: Baseline through 36 months
Overall response rate (ORR) based on International Myeloma Working Group (IMWG) uniform response criteria
次要结局
- The safety of P-BCMA-ALLO1(Baseline through 15 years)
- The anti-myeloma effect of P-BCMA-ALLO1 (ORR) in Phase 1 Parts 1 and 2(Baseline through 15 years)
- The safety of P-BCMA-ALLO1(Baseline through 15 years)
- The anti-myeloma effect of P-BCMA-ALLO1 (ORR) in Phase 1 Parts 1 and 2(Baseline through 15 years)
- Safety and Efficacy (anti-myeloma effect) will be used to guide the selection of RP2D(Baseline through 15 years)