A Single Arm, Open-Label Pilot Study of ABT-199 (Venetoclax) for Cutaneous T Cell Lymphoma (CTCL) Stage IB to IV
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Body Temperature
研究概览
简要总结
The objective of this study are to evaluate the safety and tolerability of ABT-199 (venetoclax) in patients with advanced Cutaneous T cell lymphoma (CTCL). A secondary objective is to explore clinical response to ABT-199 (venetoclax) in patients with advanced CTCL.
详细描述
This is a single arm, open-label, non-randomized study with venetoclax (ABT-199) in CTCL patients (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed mycosis fungoides). This study is planned to be conducted in 18 patients, 18 years or older in age, undergoing a 5-week dose escalation protocol (per the US FDA package insert guidelines of venetoclax for CLL). Safety monitoring will continue throughout the whole period of drug administration and the treatment will be discontinued if intolerable toxicity (defined in Stopping Rules) or disease progression occurs during this period.
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
- •Biopsy-confirmed CTCL (subtypes mycosis fungoides and Sézary syndrome only, and excluding transformed mycosis fungoides), stage IB-IV (hereafter referred to as advanced stage). An off-site biopsy report confirming CTCL diagnosis is acceptable.
- •All subjects must have shown disease refractory to one or more standard systemic therapy (PUVA, oral bexarotene, vorinostat, romidepsin, and/or Photopheresis) and/or total skin electron beam therapy over 3 months, or have demonstrated relapsed or progressive disease at any time while receiving one or more of therapies.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤
- •Adequate bone marrow function: WBC > 2000/µL; platelet count > 75,000/mm3; Neutrophil count > 1000/µL, without use of colony stimulating factors (CSF).
- •Required washout period for prior therapies
- •Spot Skin Radiation Therapy (≤10% skin surface): 4 weeks
- •Systemic therapy: 4 weeks, or until recovered from toxicities
- •Women of child-bearing potential must have negative serum pregnancy test and use accepted highly effective methods of birth control throughout the study and for 90 days after dosing and must agree to use effective contraception, such as hormonal birth control (must be at least 3 years without complications), intrauterine devices, double barrier method (condom plus spermicide or diaphragm), or abstain from sexual intercourse.
- •Male patients must be willing to use an appropriate method of contraception (e.g., condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception during the study and for 90 days after dosing.
- •Adequate hepatic function: bilirubin ≤1.5 x upper limit of normal (ULN), AST ≤3.0 x ULN, ALT ≤ 3.0 x ULN
- •Adequate renal function: creatinine clearance ≥ 50 mL/min
- •Ability to comply with the treatment schedule
排除标准
- •Extracutaneous disease except blood, bone marrow and lymph nodes.
- •Concomitant use of any systemic anti-cancer therapy or immune modifier.
- •Concomitant use of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of study drug administration.
- •Patients receiving P-gp inhibitors are not eligible for inclusion unless these agents are discontinued for a washout period of 4 weeks. Patients who are taking medications that are narrow window index P-gp substrates (e.g. digoxin, fexofenadine, loperamide, quinidine, talinolol, vinblastine) are not eligible for enrollment.
- •Patients with biopsy confirmed transformed MF.
- •Prior allogeneic hematopoietic cell transplant.
- •Any ongoing infection requiring antibiotics within 2 weeks prior to the start of the study drug, except for antibiotics (e.g. cephalexin) prescribed superficial skin infection.
- •Known history of human immunodeficiency virus (HIV), hepatitis B or C.
- •History of prior malignancy with the exception of cervical intraepithelial neoplasia, non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA <1.0). Patients with a history of other malignancies must have undergone potentially curative therapy and have no evidence of that disease for five years.
- •Uncontrolled intercurrent illness, condition, or circumstances that could limit compliance with the study including, but not limited to, the following: acute or chronic graft versus host disease, uncontrolled diabetes mellitus or hypertension, or psychiatric conditions.
- •Major surgery within 8 weeks of enrollment.
- •Medically significant cardiac event or unstable cardiovascular function defined as:
- •Symptomatic ischemia, unstable angina pectoris
- •Uncontrolled clinically significant cardiac arrhythmia
- •Symptomatic heart failure NYHA Class ≥ 3
- •Myocardial infarction or cardiac surgery within 6 months prior to enrollment
- •Cerebrovascular event (transient ischemic attack, stroke or CNS bleeding) within the last 12 months.
- •Major bleeding within the last 6 months.
- •Use of any investigational agents within 30 days prior to enrollment and for the duration of the study.
- •Pregnant or lactating.
- •Unwilling or unable to provide informed consent.
研究组 & 干预措施
ABT-199 (Venetoclax)
Patients with Cutaneous T Cell Lymphoma (CTCL) will receive ABT-199 (Venetoclax).
干预措施: ABT-199 (venetoclax) (Drug)
结局指标
主要结局
Body Temperature
时间窗: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of body temperature.
Blood Pressure- Diastolic
时间窗: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of blood pressure.
Respiratory Rate
时间窗: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of respiratory rate.
Pulse Rate
时间窗: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of pulse rate.
Adverse Events
时间窗: Up to 32 weeks
Adverse events will be used to measure the study defined outcome:Toxicity. Toxicity (as adverse events) will measured according to the NCI CTCAE (v5.0) for AEs and clinical laboratory profile; AEs will be collected in all patients who received at least one dose of venetoclax and up to four weeks after last dose (Termination visit).
Blood Pressure- Systolic
时间窗: Up to 32 weeks
Safety and tolerability endpoints will be evaluated on the basis of blood pressure.
次要结局
- Skin Clinical Response(Up to 32 weeks)
- Duration of Response(Up to 32 weeks)
- Relapse Free and Progression Free Survival(Up to 32 weeks)