A Phase 1B, Multi-Center, Open-Label Study of Novel Combinations of CC-122, CC-223, CC-292, and Rituximab in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 174
- 试验地点
- 16
- 主要终点
- Safety
研究概览
简要总结
First study, at multiple clinical centers, exploring the effects of different combinations of compounds (CC-122, CC-223 ,CC-292 and rituximab) to treat Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma
详细描述
Study CC-122-DLBCL-001 is a Phase 1b dose escalation and expansion clinical study of CC 122, CC-223 and CC-292 administered orally as doublets with or without rituximab, in participants with relapsed/refractory DLBCL who have failed standard therapy.
In expansion phase, selected combination will be administered to lenalidomide naïve FL participants and lenalidomide exposed FL participants in addition to relapsed/refractory DLBCL participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Men and women, 18 years or older, with histologically or cytologically-confirmed either:
- •Chemo-refractory DLBCL (including transformed low grade lymphoma)
- •Lenalidomide naïve; relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) following at least one prior standard systemic treatment regimen including systemic chemo-, immune-; or chemo-immunotherapy and at least one prior line of salvage therapy with no prior exposure to lenalidomide, or double-refractory FL participants with no prior exposure to lenalidomide (FL-1 cohort)
- •Lenalidomide exposed: relapsed or refractory CD20-positive follicular lymphoma (Grade 1, 2, or 3a) previously treated with at least two cycles of lenalidomide-containing regimen (FL-2 cohort), either as a single agent or in combination
- •At least one site of measurable disease
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or
- •Participants must have the following laboratory values:
- •Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L or ≥ 1.0 x 109/L (with bone marrow involvement with DLBCL)
- •Hemoglobin (Hgb) ≥ 8 g/dL.
- •Potassium within normal limits
- •Asparate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and Alanine Aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 X ULN if liver tumor is present.
- •Serum bilirubin ≤ 1.5 x ULN.
- •Estimated serum creatinine clearance of ≥ 50 mL/min
- •Participants must have the following laboratory values:
- •Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if participants received pegfilgrastim).
- •Males enrolled into treatment arms receiving CC-122 must: Agree to abstain from donating sperm while taking IP and for at least 95 days following discontinuation of IP
排除标准
- •Symptomatic central nervous system involvement.
- •Known symptomatic acute or chronic pancreatitis.
- •Persistent diarrhea or malabsorption despite medical management.
- •Peripheral neuropathy ≥ grade 2
- •Impaired cardiac function or clinically significant cardiac diseases
- •Participants with diabetes on active treatment (for participants treated on CC-223 containing arms only)
- •Prior autologous stem cell transplant (ASCT) ≤ 3 months before first dose.
- •Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning.
- •Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks prior to starting study drugs, whichever is shorter.
- •Participants who have undergone major surgery ≤ 2 weeks prior to starting study drugs.
- •Women who are pregnant or breast feeding. Adults of reproductive potential not willing to employ two forms of birth control.
- •Participants with known HIV infection, chronic active hepatitis B or C virus (HBV/HCV) infection.
- •Participants with treatment-related myelodysplastic syndrome.
- •History of concurrent second cancers requiring active, ongoing systemic treatment.
- •Prior treatment with a dual mTORC1/mTORC2 inhibitor (CC-223 arms only) or BTK inhibitor (PCI-32765) (CC-292 arms only). [Prior treatment with rapamycin analogues, PI3K or AKT inhibitors, lenalidomide and rituximab are allowed].
研究组 & 干预措施
CC-122 + CC-223 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
干预措施: CC-122 (Drug)
CC-122 + CC-223 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
干预措施: CC-223 (Drug)
CC-122 + CC-223 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
干预措施: Rituximab (Drug)
CC-122 + CC-292 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-292 administered orally twice daily at 500 mg with or without Rituximab administered by IV once every 28 days
干预措施: CC-122 (Drug)
CC-122 + CC-292 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-292 administered orally twice daily at 500 mg with or without Rituximab administered by IV once every 28 days
干预措施: CC-292 (Drug)
CC-122 + CC-292 +/- rituximab
CC-122 administered orally once daily at 2mg or 3 mg in combination with CC-292 administered orally twice daily at 500 mg with or without Rituximab administered by IV once every 28 days
干预措施: Rituximab (Drug)
CC-292 + CC-223 +/- rituximab
CC-292 administered twice daily at 500 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
干预措施: CC-223 (Drug)
CC-292 + CC-223 +/- rituximab
CC-292 administered twice daily at 500 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
干预措施: CC-292 (Drug)
CC-292 + CC-223 +/- rituximab
CC-292 administered twice daily at 500 mg in combination with CC-223 administered orally once daily at 20mg or 30 mg with or without Rituximab administered by IV once every 28 days
干预措施: Rituximab (Drug)
CC-122 + rituximab
CC-122 administered orally once daily in combination with Rituximab.
干预措施: CC-122 (Drug)
CC-122 + rituximab
CC-122 administered orally once daily in combination with Rituximab.
干预措施: Rituximab (Drug)
结局指标
主要结局
Safety
时间窗: From the time of informed consent, throughout dosing period and for 28 days after the last dose of study drug.
To determine safety profiles and dose-limiting toxicities of study drug combinations using NCI CTCAE v4.
次要结局
- Pharmacokinetics - CC-223 and CC-292 interaction(Day 1, Day 15)
- Efficacy(Every 2-3 months until proof of tumor progression)