A Phase I, Multi Center, Open Label Study of CC-98633, BCMA Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed and/or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 78
- 试验地点
- 11
- 主要终点
- Adverse Events (AEs)
研究概览
简要总结
This is a Phase 1, multicenter, open-label study of CC-98633, BCMA-Targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in participants with relapsed and/or refractory multiple myeloma.
The study will consist of 2 parts: dose-escalation (Part A) and dose-expansion (Part B). The dose-escalation part (Part A) of the study is to evaluate the safety and tolerability of increasing dose levels of CC-98633 to establish a recommended Phase 2 dose RP2D(s); and the dose-expansion part (Part B) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of CC-98633 at the RP2D(s).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Age ≥ 18 years.
- •Signed written informed consent prior to any study procedure.
- •Relapsed and/or refractory multiple myeloma (MM).
- •Subjects must have documented progressive disease as per International Myeloma Working Group (IMWG) criteria during or within 12 months of completing treatment with the last anti-myeloma treatment regimen before study entry. Also, subjects with confirmed progressive disease within 6 months prior to start of Screening and who are refractory (or non-responsive) to their most recent anti-myeloma treatment regimen afterwards will be also eligible.
- •Part A and Part B Cohort A: Subjects must have confirmed at least 3 prior antimyeloma treatment regimens.
- •Part B Cohort B only: Subjects must have received at least 1 but no greater than 3 prior antimyeloma treatment regimens, including a proteasome inhibitor and immunomodulatory agent.
- •Subjects must have previously received all of the following therapies:
- •i) Autologous stem cell transplant ii) A regimen that included an immunomodulatory agent (eg, thalidomide, lenalidomide, pomalidomide) and a proteasome inhibitor (eg, bortezomib, carfilzomib, ixazomib), either alone or combination iii) Anti-CD38 (eg, daratumumab), either alone or combination Subjects in Cohort B do not require prior anti-CD38 antibody therapy.
- •Measurable disease
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
排除标准
- •Known active or history of central nervous system (CNS) involvement of MM
- •Active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, or clinically significant amyloidosis
- •Prior treatment with CAR T-cell or another genetically modified T-cell therapy
- •Part A and Part B Cohort A only: Prior treatment with investigational therapy directed at BCMA
- •Uncontrolled or active infection
- •Active autoimmune disease requiring immunosuppressive therapy
- •History or presence of clinically significant CNS pathology such as seizure disorder, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
研究组 & 干预措施
CC-98633
Subjects will receive CC-98633 following 3 consecutive doses of lymphodepleting chemotherapy (fludarabine and cyclophosphamide).
干预措施: CC-98633 (Biological)
结局指标
主要结局
Adverse Events (AEs)
时间窗: From the time of informed consent and follow up to 2 years after infusion of CC-98633:
incidence and severity of AEs. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
次要结局
- Pharmacokinetics - maximum serum concentration (Cmax)(Up to 2 years after CC-98633 infusion)
- Pharmacokinetics -time to peak serum concentration (tmax)(Up to 2 years after CC-98633 infusion)
- Complete Response (CR) Rate(Up to 2 years after CC-99633 infusion)
- Time to response (TTR)(Up to 2 years after CC-98633 infusion)
- Progression free survival (PFS)(Up to 2 years after CC-98633 infusion)
- Overall survival (OS)(Up to 2 years after CC-98633 infusion)
- Very good partial response (VGPR) or better(Up to 2 years after CC-98633 infusion)
- Duration of response (DOR)(Up to 2 years after CC-98633 infusion)
- Pharmacokinetics - Area under curve (AUC)(Up to 2 years after CC-98633 infusion)
- Overall Response Rate (ORR)(Up to 2 years after CC-98633 infusion)
- Time to complete response (TTCR)(Up to 2 years after CC-98633 infusion)