A Phase I Trial Assessing the Feasibility of Romidepsin Combined With Brentuximab Vedotin for Patients Requiring Systemic Therapy for Cutaneous T-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This is a Phase I Trial to assess the feasibility of Romidepsin combined with Brentuximab Vedotin for patients requiring Systemic Therapy for Cutaneous T-cell Lymphoma.
详细描述
This is a traditional "3+3" phase 1 dose de-escalation design testing up to 3 dose levels of romidepsin in conjunction with brentuximab vedotin in patients with untreated or previously treated (up to 2 prior systemic regimens, including photopheresis) CTCL. Dose-limiting toxicities (DLT) will be determined during cycle 1. The first 3 subjects will begin at dose level 1. If no DLT is encountered another 3 subjects will be enrolled at the same dose level. The maximum tolerated dose (MTD) will be the dose level at which ≤ 1 of 6 of subjects experience DLT. If more than one subject at any one dose level encounters a DLT, the dose will be de-escalated for all subsequent subjects. Should no DLTs occur, the investigators will not escalate beyond dose level 1. Once the MTD has been confirmed, the investigators will enroll an additional 9 patients in a toxicity refinement cohort for a total of 15 evaluable patients at the MTD.
Treatment will continue for up to 16 cycles (one cycle is 28 days) or until disease progression or toxicities, whichever occurs first. Drugs can be continued after 16 cycles if a patient has derived a clinical benefit from treatment after discussion with the sponsor-investigator.
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
- •Patients must have histologically or cytologically confirmed diagnosis of mycosis fungoides (MF), Sezary syndrome (SS) or primary cutaneous CD30-positive lymphoproliferative disorder, including lymphomatoid papulosis and primary cutaneous ALCL (pc-ALCL)as defined by the WHO classification of Tumors of Hematopoietic and Lymphoid tissue.
- •Please note that tumor samples for patients with MF or SS can be CD30 negative and do not have to be CD30 positive on either flow cytometry or immunohistochemistry for patients to be eligible.
- •Patients with MF/SS must have stage IB, IIA, IIB, III or IV disease; patients with primary cutaneous CD30-positive lymphoproliferative disorder must have multifocal symptomatic or extensive lesions requiring systemic treatment.
- •Patients must require systemic treatment.
- •Patients can have received up to 2 lines of systemic treatment. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy.
- •Age > 18 years.
- •ECOG performance status 0, 1 or
- •Patients must have acceptable organ and marrow function as defined below:
- •Absolute neutrophil count > 1,500/mcL
- •Platelets > 100,000/mcL
- •Total bilirubin within normal institutional limits
- •AST/ALT (SGOT/SGPT) < 2 times institutional normal limits
- •Creatinine within normal institutional limits OR
- •Creatinine clearance > 60 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal
- •Women of child-bearing potential (WOCBP) must have a negative pregnancy test
- •Ability to understand and willingness to sign a written informed consent and HIPAA consent document.
- •Patients with HIV who are not receiving cytochrome p450 inhibitors, and who have a minimum of 300+ CD4+ cells/mm3, an undetectable viral load, and no history of AIDS indicator conditions.
排除标准
- •Patients who have not had resolution of clinically significant toxic effects of prior anticancer therapy to ≤grade 1 as per by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0).
- •Grade 2 or greater neuropathy.
- •Patients may not be receiving any other investigational agents.
- •Patients with known CNS involvement.
- •Patients must not receive concurrent systemic or topical steroids or other skin directed therapy while on study except as outlined in 5.2.2
- •Patients who have experienced allergic reactions to monoclonal antibodies.
- •Patients who have received prior HDAC inhibitors, or brentuximab vedotin, except for patients who were exposed to above drugs only for a short time (less than 8 weeks), did not progress while on treatment, and did not have intolerable toxicity but were discontinued for another reason (e.g., comorbidity) may be permitted to enter the study after discussion with the sponsor-investigator.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant or breast feeding. Refer to section 4.4 for further detail.
- •Second malignancies that require active treatment with the exception of breast or prostate cancer on endocrine therapy.
研究组 & 干预措施
Treatment
Treatment consists of the combination of Romidepsin given 10mg/m2 or 14mg/m2 on days 1, 8 and 15 every 28 days and Brentuximab vedotin given 0.9mg/kg or 1.2mg/kg on days 1 and 15 every 28 days for 16 cycles.
干预措施: Romidepsin (Drug)
Treatment
Treatment consists of the combination of Romidepsin given 10mg/m2 or 14mg/m2 on days 1, 8 and 15 every 28 days and Brentuximab vedotin given 0.9mg/kg or 1.2mg/kg on days 1 and 15 every 28 days for 16 cycles.
干预措施: Brentuximab vedotin (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: during treatment period which is an average of 64 weeks.
CTCAE v4.03
Dose-limiting toxicities (DLTs)
时间窗: during the first 28 days (cycle 1) of treatment
CTCAE v4.03
次要结局
- Estimate complete and partial response rate of the combination treatment(64 weeks, 30 days post treatment and every 12 weeks post-treatment, up to 2 years)
- Progression free survival (PFS)(From the time of patient registration until disease progression, measured every 12 weeks up to 2 years)
- overall safety and tolerability of the combination of brentuximab vedotin & romidepsin assessed by adverse events.(from start of treatment to 30 days post treatment period (16 cycles))
- Overall survival (OS)(From the time of patient registration until death, measured every 12 weeks up to 2 years)