A Phase I/II Study of RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 5
- 主要终点
- determination of the maximum tolerable dose and evaluation of response rate
研究概览
简要总结
The urgent need for new effective therapy for T-cell lymphoma patients and promising results observed so far in trials with RAD001(everolimus, mTOR inhibitor) strongly warrants the investigation of RAD001 combined with CHOP as a first-line treatment in peripheral T-cell lymphoma patients.
Thus, we designed a phase I/II study with the combination of RAD001 with CHOP chemotherapy for newly diagnosed peripheral T-cell lymphoma patients.
Phase I
- Primary objective
: To define the maximum tolerable dose 2. Secondary objective
- To evaluate the dose-limiting toxicity
- To evaluate the pharmacokinetics of RAD001
- Pharmacogenomic profiling
Phase II
- Primary objective
: To evaluate the overall response rate 2. Secondary objective
- To estimate the time to progression
- To estimate overall survival
- Pharmacogenomic profiling
详细描述
Phase I Level 1: RAD001 2.5 mg PO daily D1-14 + CHOP Level 2: RAD001 5 mg PO daily D1-14 + CHOP Level 3: RAD001 7.5 mg PO daily D1-14 + CHOP Level 4: RAD001 10 mg PO daily D1-14 + CHOP CHOP every 3 weeks D1 Cytoxan 750mg/m2 + D5W 100ml MIV over 1hr D1 Doxorubicin 50mg/m2 + D5W 100ml MIV over 30mins D1 Vincristine 1.4mg/m2 (max.2mg) IV push D1-D5 Prednisolone 100mg/d PO (40-30-30) Phase II Determined dosage of RAD001 + CHOP every 3 weeks Treatment will be continued until planned 6 cycles or disease progression
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven peripheral T-cell lymphoma, unspecified, (PTCL), ALK-negative anaplastic large cell T-cell lymphoma (ALCL), Angioimmunoblastic T cell lymphoma (AITL), Cutaneous T-cell lymphoma
- •Adequate organ function as defined by the following criteria:
- •A.Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) ≤2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy B.Total serum bilirubin ≤1.5 x ULN C.Absolute neutrophil count (ANC) ≥1500/µL D.Platelets ≥100,000/µL E.Hemoglobin ≥9.0 g/dL (may be transfused or erythropoietin treated) F.Serum calcium ≤12.0 mg/dL G.Serum creatinine ≤1.5 x ULN
- •At least one measurable lesion
- •ECOG PS 0-2
- •Informed consent
- •Age 20 to 70 years old
排除标准
- •Prior radiation therapy or surgery within 4 weeks prior to study entry
- •History of central nervous system (CNS) metastases
- •Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥
- •Pregnancy or breastfeeding.
- •Hepatitis B virus surface antigen positive
- •Extranodal NK/T cell lymphoma
- •Mycosis fungoides
- •ALK-positive Anaplastic large cell lymphoma
研究组 & 干预措施
RAD001-CHOP
Prospective multicenter open-label phase I/II study Phase I: RAD001 2.5 - 10 mg PO daily D1-14 + CHOP every 3 weeks Phase II: Determined dosage of RAD001 + CHOP every 3 weeks Treatment will be continued until planned 6 cycles or disease progression
干预措施: RAD001 (Everolimus) (Drug)
结局指标
主要结局
determination of the maximum tolerable dose and evaluation of response rate
时间窗: Phase I for maximal tolerable dose and phase II for efficacy
次要结局
- doe-limiting toxicity and pharmacogenomics(Phase I/II)
研究者
Kim, Seok Jin
Associate professor
Samsung Medical Center