A Phase 2 Single Center, Single Arm, Open Label Mogamulizumab Combined Upfront With Low Dose Total Skin Electron Beam Therapy (LD TSEBT) in Patients With Mycosis Fungoides (MF) and Sézary Syndrome (SS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
The purpose of this study is to determine the efficacy of the combination of LD-TSEBT and mogamulizumab in patients with MF and SS. And to evaluate the secondary measures of clinical benefit of the combination therapy and to evaluate the safety and tolerability of the combination in patients with MF and SS.
详细描述
Primary Objective:To determine the efficacy of the combination of LD TSEBT and mogamulizumab in patients with MF and SS
Secondary Objective: To evaluate the secondary measures of clinical benefit of the combination therapy and to evaluate the safety and tolerability of the combination in patients with MF and SS
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
- •Stages IB-IV MF or SS
- •Stages IB-IV MF or SS
- •At least 1 prior standard-of-care therapy
- •Prior LD-TSEBT (> 3 months prior) and prior mogamulizumab is allowed, as long as progressive disease (PD) did not occur while on therapy, and did not discontinue due to toxicities
- •≥ 18 years of age
- •ECOG performance status of 0 to 2
- •All clinically-significant toxic effects of prior cancer therapy resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE, v 5.0).
- •MF and a known history of non-complicated staphylococcus colonization/infection is eligible provided that stable doses of prophylactic antibiotics continue.
- •The following minimum wash-out from previous treatments are required (prior to 1st day of treatment), if applicable.
- •≥ 2weeks for retinoids, interferons, Vorinostat, romidepsin, pralatrexate, or other systemic anti-cancer/CTCL therapies
- •≥ 2 weeks for phototherapy, local radiation therapy
- •≥ 2 weeks for topical therapy (including topical steroid, retinoid, nitrogen mustard, or imiquimod)
- •≥ 12 weeks for total skin electron beam therapy
- •> 12 weeks for alemtuzumab
- •Rapidly progressive malignant disease may be enrolled prior to above periods after discussion with the Protocol Director.
- •Adequate hematologic function
- •Absolute neutrophil count (ANC) ≥ 1,000 cells/μL (≥ 1,000/mm3)
- •Platelets ≥ 75,000 cells/μL (≥ 75,000/mm3).
- •Adequate hepatic function
- •Bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN). Exception: If Gilbert's syndrome; then ≤ 5 times ULN.
- •Aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 x ULN; or ≤ 5.0 x ULN in the presence of known hepatic involvement by CTCL.
- •Adequate renal function
- •Calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula.
- •If prior allogeneic hematopoietic stem cell transplant (HSCT), then must be free of graft-vs-host disease (GvHD) and receiving immunosuppressive therapy.
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test.
- •WOCBP must agree to use effective contraception during the study and for 3 months after the last dose.
- •Male participants and their female partners of child bearing potential must be willing to use an appropriate method of contraception during the study and for 3 months after the last dose.
排除标准
- •MF with limited disease (Stage IA) or central nervous system (CNS) disease
- •Concomitant corticosteroid use. (with the exception that topical steroid and oral prednisone are allowed at ≤ 20 mg/day, if patient has been on a stable dose for at least 2 weeks prior to 1st day of treatment)
- •Pregnant or breastfeeding
- •Active autoimmune disease or history deemed by the investigator to be clinically significant
- •Known human immunodeficiency virus (HIV) positivity; or active hepatitis B or C.
- •Active herpes simplex or herpes zoster. Those receiving prophylaxis for herpes and who started taking medication at least 30 days prior to the Screening Visit, and have no active signs of active infection, and whose last active infection was more than 6 months ago, may enter the study, and should continue to take the prescribed medication for the duration of the study.
研究组 & 干预措施
LD TSEBT
Mogamulizumab with low dose total skin electron beam therapy. •
LD (12 Gy) TSEBT will be initiated on Cycle 1 Day 2 (± 2 days) of mogamulizumab over 2 to 3 week period per standard of care (SOC), as tolerated. Mogamulizumab (1 mg/kg) will be administered over 60 minutes as follows (per SOC and FDA approved use in MF and SS):
- Cycle 1 only: Days1; 8; 15; and 22 (± 2 days)
- Cycle 2 and beyond: Day 1 and Day 15 (± 3 days)
干预措施: LD TSEBT (Radiation)
LD TSEBT
Mogamulizumab with low dose total skin electron beam therapy. •
LD (12 Gy) TSEBT will be initiated on Cycle 1 Day 2 (± 2 days) of mogamulizumab over 2 to 3 week period per standard of care (SOC), as tolerated. Mogamulizumab (1 mg/kg) will be administered over 60 minutes as follows (per SOC and FDA approved use in MF and SS):
- Cycle 1 only: Days1; 8; 15; and 22 (± 2 days)
- Cycle 2 and beyond: Day 1 and Day 15 (± 3 days)
干预措施: Mogamulizumab (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 12 months
Response to treatment will be assessed as the number and proportion of participants who achieve either a complete response (CR) or partial response (PR). The outcome is reported as numbers without dispersion. Clinical response will be assessed as follows. * CR: Complete disappearance of all clinical evidence of disease * PR: Decrease in size or amount of measurable disease lesions * Progressive disease (PD): Worsening of lesions; appearance of new lesions; or recurrence of lesions * Stable disease (SD): Disease status that is neither CR, PR, nor PD.
次要结局
- Time-to-Next Significant Treatment (TTNT)(3 years)
- Treatment-related Adverse Events ≥ Grade 3(12 months)
- Progression free survival (PFS)(3 years)
- Duration of response (DOR)(3 years)
- Patient reported Quality of Life (QoL)(3 years)
- Proportion of Participants With ≥4, ≥6, and ≥12 Months of Response Duration (ORR4, ORR6, and ORR12)(12 months)
- Time-to-Next Significant Treatment (TTNT)(3 years)
- Patient reported Quality of Life (QoL)(3 years)
- Treatment-related Adverse Events ≥ Grade 3(12 months)