A Phase 1/2, Multi-center, Open-label Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of an Orally Available Small Molecule, CC-99282, Alone and in Combination With Anti-Lymphoma Agents in Subjects With Relapsed or Refractory Non-Hodgkin Lymphomas (R/R NHL).
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Celgene
- 入组人数
- 438
- 试验地点
- 129
- 主要终点
- Number of participants with left ventricular ejection fraction (LVEF) assessment abnormalities
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of CC-99282 alone and in combination with anti-lymphoma agents in participants with relapsed or refractory non-Hodgkin's lymphomas.
详细描述
Participants with relapsed or refractory non-Hodgkin's lymphomas (R/R NHL) who have failed at least 2 lines of therapy (or have received at least one prior line of standard therapy and are not eligible for any other therapy).
The dose escalation will evaluate the safety and tolerability of escalating doses of CC-99282 in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) and/or relapsed or refractory follicular lymphoma (R/R FL) participants to determine the maximum tolerated dose (MTD) of CC-99282 as monotherapy.
The dose expansion will further evaluate the safety and preliminary efficacy of single agent CC-99282 or the safety and preliminary efficacy of CC-99282 in combination with anti-lymphoma agents in participants with R/R DLBCL and NHL.
Part B Cohort B will further evaluate the potential effects of food on the PK and safety of CC-99282.
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
- •History of Non-Hodgkin's Lymphoma (NHL) with relapsed or refractory disease.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
排除标准
- •Life expectancy ≤ 2 months.
- •Received prior systemic anti-cancer treatment (approved or investigational) ≤ 5 half-lives or 4 weeks prior to starting CC-99282, whichever is shorter.
- •Is on chronic systemic immunosuppressive therapy or corticosteroids or has clinically significant graft-versus-host disease (GVHD).
- •Impaired cardiac function or clinically significant cardiac disease.
- •Other protocol-defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Part A: Dose Escalation
干预措施: CC-99282 (Drug)
Part B: Dose Expansion
干预措施: CC-99282 (Drug)
Part B: Dose Expansion
干预措施: Rituximab (Drug)
Part B: Dose Expansion
干预措施: Obinutuzumab (Drug)
Part B: Dose Expansion
干预措施: Tafasitamab (Drug)
Part B: Dose Expansion
干预措施: Valemetostat (Drug)
结局指标
主要结局
Number of participants with left ventricular ejection fraction (LVEF) assessment abnormalities
时间窗: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
Incidence of Adverse Events (AEs)
时间窗: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
Number of participants with vital sign abnormalities
时间窗: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
Number of participants with laboratory abnormalities
时间窗: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
Maximum tolerated dose (MTD)
时间窗: Up to 28 days in cycle 1
Number of participants with Eastern Cooperative Oncology Group (ECOG) performance status abnormalities
时间窗: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
Number of participants with electrocardiogram (ECG) abnormalities
时间窗: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
Dose Limiting Toxicity (DLT)
时间窗: Up to 28 days in Cycle 1
Number of participants with physical examination abnormalities
时间窗: From the time of consent at screening until 28 days after the subject discontinued study treatment (up to 4 years)
次要结局
- Pharmacokinetics - Terminal-phase elimination half-life (T-HALF)(Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
- Pharmacokinetics - Apparent total body clearance of the drug from the plasma (CLT/F)(Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
- Pharmacokinetics: Apparent volume of distribution (Vz/F)(Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
- Pharmacokinetics - Maximum plasma concentration of drug (Cmax)(Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
- Pharmacokinetics - Area under the plasma concentration-time curve (AUC)(Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
- Pharmacokinetics - Time to peak (maximum) plasma concentration (Tmax)(Cycle 1 to Cycle 4 Day 15 (each cycle is 28 days))
- Objective response rate (ORR)(Up to approximately 6 years)
- Time to response (TTR)(Up to approximately 6 years)
- Duration of response (DoR)(Up to approximately 6 years)
- Progression free survival (PFS)(Up to approximately 6 years)
- TTR(Up to approximately 4 years)
- PFS(Up to approximately 4 years)
- OS(Up to approximately 4 years)
- Overall survival (OS)(Up to approximately 6 years)
- ORR(Up to approximately 4 years)
- DOR(Up to approximately 4 years)