A Phase 1B, Multicenter, Open-label Study to Determine the Safety, Pharmacokinetics and Preliminary Efficacy of CC-99282 in Combination With Obinutuzumab in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 16
- 试验地点
- 15
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
CC-99282-CLL-001 study is a Phase IB dose escalation and expansion clinical study of CC-99282 administered in combination with Obinutuzumab in subjects with relapsed or refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
详细描述
All eligible subjects must be relapsed or refractory to at least 2 prior lines of therapy, one of which must have included an inhibitor of B-cell receptor signaling (approved Bruton's tyrosine kinase inhibitor [BTKi] or Phosphoinositide 3-kinase inhibitor [PI3Ki]) or venetoclax. The dose escalation (Part A) will evaluate the safety, tolerability, and PK of escalating doses of CC-99282 given in combination with intravenous obinutuzumab to determine the MTD and RP2D of CC-99282 when given in combination with obinutuzumab. The dose expansion (Part B) may occur at the MTD established in the dose escalation phase, or at an alternative tolerable dosing schedule, based on review of safety, PK and PD data from Part A.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Subject is ≥18 years of age
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Must have a documented diagnosis of CLL/SLL requiring treatment (IwCLL Guidelines for the Diagnosis and Treatment of CLL). In addition presence of clinically measurable disease determined by at least one of the factors listed:
- •nodal lesion that measures ≥ 1.5 cm in longest dimension (LD) and ≥ 1.0 cm in longest perpendicular dimension (LPD), or
- •spleen that measures ≥ 14 cm in longest vertical dimension (LVD) with a minimum of 2 cm enlargement, or
- •liver that measures ≥ 20 cm in LVD with a minimum of 2 cm enlargement, or
- •peripheral blood B lymphocyte count > 5000/uL
- •All eligible subjects must be relapsed after or be refractory to >2 prior lines of therapy one of which must have included an approved BTK inhibitor.
- •Must meet the following laboratory parameters:
- •Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3 or ≥ 1000 cells/mm^3 if secondary to bone marrow involvement by disease, without growth factor support for 7 days (14 days if pegfilgastrim).
- •Platelet count ≥ 75,000 cells/mm^3 (100 x 10^9/L) or ≥ 50,000 cells/mm^3 (50 x 10^9/L) if secondary to bone marrow involvement by disease, without transfusion for 7 days.
- •Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) < 3.0 x upper limit of normal (ULN).
- •Serum bilirubin < 1.5 x ULN unless due to Gilbert's syndrome.
- •Calculated creatinine clearance of ≥ 60 ml/min.
排除标准
- •Presence of any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Prior allogeneic stem cell transplant (SCT)/bone marrow transplant within 12 months of signing the ICF. Subjects who received allogeneic SCT ≥ 12 months before signing the ICF may be eligible provided there is no ongoing graft-versus-host disease and no ongoing immune suppression therapy.
- •Subject has received prior CAR-T or other T-cell targeting treatment (approved or investigational) ≤ 4 weeks prior to starting CC-
- •Subject has received prior therapy with CRBN-modulating drug (eg, lenalidomide, avadomide/CC-122, pomalidomide) ≤ 4 weeks prior to starting CC-
- •History of second malignancies with life expectancy of ≤ 2 years or requirement of therapy that would confound study results.
- •Peripheral neuropathy ≥ Grade
- •History of hypersensitivity to lenalidomide, pomalidomide, thalidomide.
- •Impaired cardiac function or clinically significant cardiac disease.
- •Persistent diarrhea or malabsorption ≥ NCI CTCAE Grade 2, despite medical management.
- •Active disease transformation (ie, Richter's Syndrome)
- •Uncontrolled/active autoimmune hemolytic anemia or thrombocytopenia
研究组 & 干预措施
CC-99282 + obinutuzumab
Escalating doses of CC-99282 administered orally once daily on intermittent schedules with obinutuzumab IV infusion 1000 mg up to 2 years in Part A. CC-99282 administered orally once daily at MTD or alternative tolerating dosing schedule with obinutuzumab IV infusion 1000 mg up to 2 years in Part B.
干预措施: CC-99282 (Drug)
CC-99282 + obinutuzumab
Escalating doses of CC-99282 administered orally once daily on intermittent schedules with obinutuzumab IV infusion 1000 mg up to 2 years in Part A. CC-99282 administered orally once daily at MTD or alternative tolerating dosing schedule with obinutuzumab IV infusion 1000 mg up to 2 years in Part B.
干预措施: Obinutuzumab (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Up to Cycle 2 Day 14 (each cycle is 28 days
The highest dose of CC-99282 in combination with obinutuzumab associated with acceptable safety and tolerability
Adverse Events (AEs)
时间窗: From first subjects first visit until 28 days after last subject discontinued study treatment
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.
Dose Limiting Toxicity (DLT)
时间窗: Up to Cycle 2 Day 14 (each cycle is 28 days)
Number of subjects with a DLT
次要结局
- Pharmacokinetics - Cmax(Up to Cycle 2 Day 14 (each cycle is 28 days))
- Pharmacokinetics - AUC(Up to Cycle 2 Day 14 (each cycle is 28 days))
- Pharmacokinetics - T-HALF(Up to Cycle 2 Day 14 (each cycle is 28 days))
- Pharmacokinetics - Vz/F(Up to Cycle 2 Day 14 (each cycle is 28 days))
- Partial response with lymphocytosis (PRL)(Up to approximately 3 years)
- Pharmacokinetics - CLT/F(Up to Cycle 2 Day 14 (each cycle is 28 days))
- Objective response rate (ORR)(Up to approximately 3 years)
- Overall survival(Up to approximately 3 years)
- Partial response (PR)(Up to approximately 3 years)
- Pharmacokinetics - Tmax(Up to Cycle 2 Day 14 (each cycle is 28 days))
- Duration of response (DoR)(Up to approximately 3 years)
- Progression free survival(Up to approximately 3 years)
- Complete response with incomplete marrow recovery (CRi)(Up to approximately 3 years)
- Nodular partial response (nPR)(Up to approximately 3 years)