Optimizing Dosing of Brentuximab Vedotin for Mycosis Fungoides, Sezary Syndrome, and Lymphomatoid Papulosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 58
- 试验地点
- 8
- 主要终点
- overall response
研究概览
简要总结
The purpose of this study is to test any good and bad effects of the study drug called brentuximab vedotin at a lower dose than is FDA-approved.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Mycosis fungoides (MF) and Sezary Syndrome (SS)
- •Pathologically confirmed mycosis fungoides/sezary syndrome at the enrolling institution, disease stage IB (defined as patches, plaque, or papules that involve 10% of the skin surface viscera) or higher
- •° CD30 negative mycosis fungoides patients are eligible.
- •Age ≥ 18 years
- •ECOG Performance Score ≤ 2
- •For Cohort 1, patients who have not received brentuximab vedotin are eligible.
- •For Cohort 2, patients who have previously had brentuximab vedotin for MF/SS are eligible. Patients previously treated on Cohort 1 who were discontinued due to toxicity are not eligible for Cohort
- •Previous systemic anti-cancer therapy must have been discontinued at least 2 weeks prior to treatment.
- •° See section 6.2 Subject Exclusion Criteria for guidelines regarding adjuvant and maintenance therapy for prior malignancy.
- •Topical or systemic steroids (equivalent to ≤ 10 mg/day of prednisone) may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, adrenal insufficiency, and/or unnecessary suffering, after discussion with PI.
- •If HIV+, patient must be on stable anti-retroviral treatment for 12 weeks prior to C1D1, with CD4 count >200 within 7 days prior to C1D
- •Females of childbearing potential must be on acceptable form of birth control per instutional standard.
- •Lymphomatoid papulosis (LyP)
- •Pathologically confirmed lymphomatoid papulosis at the enrolling institution
- •Requiring systemic treatment per investigator's discretion
- •Age ≥ 18 years
- •ECOG Performance Score ≤ 2
- •Previous systemic anti-cancer therapy must have been discontinued at least 2 weeks prior to treatment.
- •Topical or systemic steroids (equivalent to ≤ 10 mg/day of prednisone) may be considered if dose has been constant and discontinuation may lead to rebound flare in disease, adrenal insufficiency, and/or unnecessary suffering.
- •If HIV+, patient must be on stable anti-retroviral treatment for 12 weeks prior to C1D1, with CD4 count >200 within 7 days prior to C1D
- •Females of childbearing potential must be on acceptable form of birth control per institutional standard
排除标准
- •Concurrent use of other systemic anti-cancer agents or treatments for mycosis fungoides/sezary syndrome, or lymphomatoid papulosis.
- •Grade 2 or greater neuropathy
- •Severe renal impairment (CrCL <30 mL/min)
- •Moderate or severe hepatic impairment (Child-Pugh B or Child-Pugh C)
- •° See Appendix E for Child Pugh Classification chart
- •Women of reproductive potential† must have a negative Serum ß human chorionic gonadotropin (ß-HCG) pregnancy test within 1 week of C1D
- •They should discuss contraception with treating provider.
- •Previous use of brentuximab vedotin (for Cohort 1 ONLY)
- •Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma).
- •Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator.
- •Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy (other than T-cell lymphoma) is permissible after discussion with the MSK Principal Investigator.
- •For Cohort 2, patients who previously progressed on the standard 1.8mg/kg dose and schedule of brentuximab vedotin are ineligible.
- •A female of reproductive potential is a sexually mature female who: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).
研究组 & 干预措施
not been previously treated with brentuximab vedotin.
Patients with MF/SS who have not been previously treated with brentuximab vedotin. For MF patients: Treatment delays lasting longer than 8 weeks for toxicity will result in removal from study. As of October 2020, the Simon two stage design for Cohort 1 has restarted at the 1.2 mg/kg dose.
干预措施: brentuximab vedotin (Drug)
treated with reduced dose brentuximab vedotin
Patients with MF/SS who were previously treated with brentuximab vedotin. Up to 10 patients will be enrolled onto this cohort. Following identification of a promising dose after the completion of the full Cohort 1 Simon two stage design, enrollment will initiate onto cohort 2 at the dose found to be promising in cohort 1. For MF patients: Treatment delays lasting longer than 8 weeks for toxicity will result in removal from study. The 0.9mg/kg dose did not meet the primary endpoint for response, therefore 1.2 mg/kg has been chosen as the dose for Cohort 2. As of October 2020, enrollment on our exploratory Cohort 2 has opened at the 1.2 mg/kg dose.
干预措施: brentuximab vedotin (Drug)
Patients with LyP
Patients with LyP patients with lymphomatoid papulosis will receive brentuximab vedotin 0.9 mg/kg as an intravenous infusion over 30 minutes every three weeks. Cohort 3 will enroll patients concurrently with Cohort 1. Treatment may be held if felt to be in patient's best interest (for example: for toxicity or no active disease). Treatment can be reinitiated after discussion with MSK PI as long as the study is still open and patient has not received alternate systemic therapy.
干预措施: brentuximab vedotin (Drug)
结局指标
主要结局
overall response
时间窗: 1 year
measure best overall response during treatment by the global response score, which incorporates the mSWAT, as well as CT scan for patients with baseline nodal/visceral involvement and flow cytometry for patients with baseline positive peripheral flow cytometry
次要结局
未报告次要终点