A Phase 1 Multicenter Study of KITE-585, an Autologous Anti-BCMA CAR T-Cell Therapy, in Subjects With Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 9
- 主要终点
- Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of KITE-585, an autologous engineered chimeric antigen receptor (CAR) T-cell product targeting a protein commonly found on myeloma cells called B-cell maturation antigen (BCMA), as measured by the incidence of dose-limiting toxicities (DLTs). Participants will be given a 3 day course of conditioning chemotherapy followed by a single infusion of KITE-585.
详细描述
Participants with relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, ECG and echocardiogram of the heart, brain MRI, and blood draws. Eligible participants have white blood cells collected by leukapheresis. These cells are genetically modified to make the experimental treatment KITE-585. Participants receive conditioning chemotherapy prior to the KITE-585 infusion. After the KITE-585 infusion, participants will be followed for side effects and effect of KITE-585 on their myeloma. Study procedures may be performed while hospitalized and/or in the outpatient setting. Participants who received an infusion of KITE-585 will complete the remainder of the 15 year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968
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
- •Measurable relapsed or refractory myeloma as defined by the International Myeloma Working Group (IMWG) Consensus Criteria following treatment with at least 3 lines of therapy including with both a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or progressive myeloma that is refractory to a regimen containing both a PI and an IMiD.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
- •Absolute neutrophil count (ANC) ≥ 1,000/µL
- •Platelet count ≥ 75,000/µL
- •Absolute lymphocyte count ≥ 100/µL
- •Creatinine clearance above limits set in the protocol for each cohort
- •Normal cardiac function as assessed by electrocardiogram (ECG) and echocardiogram
- •Baseline oxygen saturation > 92% on room air and no clinically significant pleural effusion
排除标准
- •Plasma cell leukemia
- •Non-secretory multiple myeloma
- •History of Central nervous system (CNS) involvement by multiple myeloma
- •Prior CAR therapy or other genetically modified T cells
- •Inadequate washout from prior therapy
- •Autologous stem cell transplant within 6 weeks before enrollment or any history of allogenic transplant
- •History of active autoimmune disease
- •History of deep vein thrombosis or pulmonary embolism requiring systemic anticoagulation within 6 months before enrollment
- •Recent history of other (non multiple myeloma) cancer
- •Active viral, fungal, bacterial or other infection
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Dose Escalation: 3 x 10^7 KITE-585
Participants with relapsed/refractory multiple myeloma (RRMM), will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10^7 autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: KITE-585 (Genetic)
Dose Escalation: 3 x 10^7 KITE-585
Participants with relapsed/refractory multiple myeloma (RRMM), will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10^7 autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Cyclophosphamide (Drug)
Dose Escalation: 3 x 10^7 KITE-585
Participants with relapsed/refractory multiple myeloma (RRMM), will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10^7 autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Fludarabine (Drug)
Dose Escalation: 1 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: KITE-585 (Genetic)
Dose Escalation: 1 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Cyclophosphamide (Drug)
Dose Escalation: 1 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Fludarabine (Drug)
Dose Escalation: 3 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: KITE-585 (Genetic)
Dose Escalation: 3 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Cyclophosphamide (Drug)
Dose Escalation: 3 x 10^8 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 3 x 10^8 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Fludarabine (Drug)
Dose Escalation: 1 x 10^9 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10^9 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: KITE-585 (Genetic)
Dose Escalation: 1 x 10^9 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10^9 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Cyclophosphamide (Drug)
Dose Escalation: 1 x 10^9 KITE-585
Participants with RRMM, will receive conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 30 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a dose of 1 x 10^9 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants will then have a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Fludarabine (Drug)
Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585
RRMM participants with moderate renal impairment (creatinine clearance 30 to 59 mL/min [Grade 2 chronic kidney disease]) will receive a conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 24 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a tolerable dose of 3 x 10^7 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants then had a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: KITE-585 (Genetic)
Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585
RRMM participants with moderate renal impairment (creatinine clearance 30 to 59 mL/min [Grade 2 chronic kidney disease]) will receive a conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 24 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a tolerable dose of 3 x 10^7 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants then had a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Cyclophosphamide (Drug)
Dose Expansion (Renal Impairment): 3 x 10^7 KITE-585
RRMM participants with moderate renal impairment (creatinine clearance 30 to 59 mL/min [Grade 2 chronic kidney disease]) will receive a conditioning chemotherapy consisting of cyclophosphamide 300 mg/m^2/day and fludarabine 24 mg/m^2/day IV infusion for 3 days followed by a single infusion of KITE-585 at a tolerable dose of 3 x 10^7 autologous anti-BCMA CAR T cells on Day 0. Participants may also receive an optional bridging therapy at the investigator's discretion, up to 7 days before initiation of conditioning chemotherapy. Participants then had a post-treatment assessment period and long-term follow-up period from Week 2 to Month 3 and after Month 3 to Year 15, respectively.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
时间窗: From KITE-585 infusion until 28 days after KITE-585 infusion
A DLT is a KITE-585-related event with onset in the first 28 days following infusion. DLTs are defined by events and duration of events, including: * Any duration: Grade (GR) 4 cytokine release syndrome (CRS), KITE-585-related GR 5 adverse events (AE) and GR 4 nonhematologic AE with the exceptions of fever, nausea, hepatic toxicity that resolves to GR 3 or better in ≤ 72 hours, hypogammaglobulinemia, tumor lysis syndrome, acute renal toxicity requiring dialysis for ≤ 7 days, intubation for airway protection for ≤ 7 days and AE resolves to ≤ GR 1 within 2 weeks and baseline within 4 weeks * ≥ 72 hours: GR 3 CRS and GR 3 nonhematologic AE with the exceptions of fever, nausea, hepatic toxicity that resolves to GR 2 or better in ≤ 14 days, hypogammaglobulinemia and tumor lysis syndrome * ≥ 30 days: GR 4 hematologic AE with the exceptions of cytopenias attributable to ongoing or recurrent multiple myeloma
次要结局
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events(Enrollment through 24 months after treatment with KITE-585 or up to disease progression or initiation of another anti-cancer therapy, whichever occurs first (maximum: 2.9 months))
- Progression Free Survival (PFS) as Determined by Study Investigators According to the IMWG Consensus Panel 1(From KITE-585 infusion to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months))
- Overall Survival (OS)(From KITE-585 infusion to date of data cutoff (maximum: 17.6 months))
- Percentage of Participants Experiencing Clinically Significant Laboratory Abnormalities(Enrollment through 24 months after treatment with KITE-585 or up to disease progression or initiation of another anti-cancer therapy, whichever occurs first (maximum: 2.9 months))
- Objective Response Rate (ORR) as Determined by Study Investigators According to the International Myeloma Working Group (IMWG) Consensus Panel 1 Criteria(From KITE-585 infusion to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months))
- Time to Next Treatment (TTNT)(From KITE-585 infusion to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months))
- Duration of Response (DOR) as Determined by Study Investigators According to the IMWG Consensus Panel 1(From first response to the earlier date of data cutoff and first administration of other anti-cancer therapies including stem cell transplant (maximum: 17.6 months))