MOGAT: Open-Label, Phase II, Multi-Centre, Study of Anti-CCR4 Monoclonal Antibody (Mogamulizumab) and Total Skin Electron Beam Therapy (TSEB) in Patients With Stage IB-IIB Cutaneous T-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 43
- 试验地点
- 13
- 主要终点
- Progression Free Survival Rate at 48 weeks
研究概览
简要总结
Cutaneous T-Cell Lymphoma (CTCL) has a chronic, relapsing course with patients undergoing multiple, consecutive therapies. Treatment aims at the clearance of skin disease, minimization of recurrence, prevention of disease progression and preservation of quality of life.
The treatment of CTCL is primarily determined by the disease extent. Prolonged complete remissions have been obtained with skin-directed therapies in early stage Mycosis fungoides (MF) (IA-IIA), whereas advanced stages CTCL (IIB-IVB) are often refractory to treatment and, thus, have an unfavorable prognosis.
Currently, there is no standard treatment option for CTCL, especially for advanced stages, and the optimal treatment sequence is still debated with a large variability in the therapeutic approach across countries. Patients with advanced-stage disease or refractory cutaneous CTCL should be treated with systemic therapies and, whenever possible, should be offered to participate in clinical trials. Currently, there is a urgent call for new treatments in CTCL with higher response rate and prolonged time to progression;
In this study, we propose a very innovative treatment schedule in which mogamulizumab is used before Total Skin Electron Beam therapy (TSEB) for systemic disease control and as a maintenance treatment after skin-directed therapy. We hypothesize that our regimen will show a more manageable toxicity profile than a combination treatment and allow for a long-term mogamulizumab administration.
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
- •Diagnosis of MF stage IB, IIA or IIB at registration, and MF stage should have never met criteria for stage IIIA or higher.
- •Subjects who have failed (refractory or relapsed) at least one prior course of systemic therapy.
- •All clinically significant toxic effects of prior cancer therapy to grade ≤ 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE, v.5.0), excluding the specifications required in the criteria 'Adequate haematological and organ function' below
- •Males and female subjects ≥ 18 years
- •WHO performance status 0-1
- •Adequate haematological and organ function:
- •absolute neutrophil count (ANC) ≥ 1.0 × 109/L
- •platelets ≥ 75 × 109/L (≥ 75,000/mm3)
- •bilirubin ≤ 1.5 × upper limit of normal (ULN) except for subjects with Gilbert's syndrome;
- •aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN
- •serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance > 50 mL/min using the Cockcroft-Gault formula
- •Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible provided a washout period ≥ 3 months and CD4+ cell counts ≥ 200/mm3
- •Clinically normal cardiac function based on 12-lead ECG and above the institutional lower limit of normal for left ventricular ejection fraction assessed either by multi-gated acquisition scan or cardiac ultrasound
- •Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 3 days prior to the first dose of study treatment
- •WOCBP must agree to use effective contraception, defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide) or practice through abstinence from sexual intercourse during the study and for 6 months after the last dose.
- •Male subjects and their female partners of child bearing potential must be willing to use an appropriate method of contraception defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide) or practice through abstinence from sexual intercourse (periodic abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception) during the study and for 6 months after the last dose.
- •Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment
- •Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations
排除标准
- •Prior treatment with mogamulizumab, or any other anti-CCR4
- •Prior TSEB
- •Patients who received localised radiotherapy within 2 weeks prior to registration
- •Patients who received any systemic therapy for MF within 4 weeks prior to registration.
- •Note: In case of rapid progression, if patient has recovered from all toxicities AND last dose occurred more than 5 half lives of the drug/treatment used, patient could be allowed to start earlier after consultation with medical monitor
- •History of other malignancy in the past 5 years with the exception of treated carcinoma in situ of the cervix, localized prostate cancer with PSA <0.1, in-situ melanoma, and non-melanoma skin cancer
- •History of severe allergic anaphylactic reactions to chimeric, human or humanized antibodies, or fusion proteins
- •Known hypersensitivity to CHO cell products or any component of the mogamulizumab formulation (see section 6.1.1)
- •Significant uncontrolled intercurrent illness including, but not limited to:
- •uncontrolled infection requiring antibiotics;
- •clinically significant cardiac disease (class III or IV of the New York Heart Association [NYHA] classification);
- •unstable angina pectoris;
- •angioplasty, stenting, or myocardial infarction within 6 months;
- •clinically significant cardiac arrhythmia
- •Have active sign of herpes zoster
- •Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study.
- •Patients with eczema, psoriasis, lichen simplex chronicus, with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- •Rash must cover <10% of body surface area
- •Disease is well controlled at baseline and requires stable use of low to mild potency topical corticosteroids for at least 4 weeks.
- •No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 4 months.
- •Immunomodulatory drugs or high-dose systemic steroids for concomitant or intercurrent conditions other than T-cell lymphoma within 7 days of registration.
- •However, stable dose of a low dose systemic systemic corticosteroid (≤10 mg prednisone equivalent per day) or stable dose of a low potency topical corticosteroid for at least 4 weeks prior to the registration is permitted. Subjects may receive intra-articular, intraocular, inhalation or nasal corticosteroids. Initiation of treatment with corticosteroids or increase in dose while on study is not permitted except for the treatment of adverse events.
- •Patients who are planned to receive stem cell transplantation
- •Has a known history of Human T-lymphotropic virus 1 (HTLV-1), or human immunodeficiency virus (HIV) (test to be performed within 21 days of registration if allowed by local legislation)
- •Has known active Hepatitis B or Hepatitis C
- •Note: patient will be eligible if:
- •Negative hepatitis B surface antigen (HBsAg) test at screening
- •Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening . The HBV DNA test will be performed only for patients who have a positive total HBcAb test.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
研究组 & 干预措施
Mogamulizumab + Total Skin Electron Beam Therapy (TSEB)
Treatment with mogamulizumab will be continued until disease progression or the occurrence of another withdrawal criterion as specified in the protocol.
TSEB will start 28 days after mogamulizumab cycle 2 day 1 at a dose of 12 Gy in 8 fractions over two weeks (4 fractions per week).
干预措施: Mogamulizumab (Drug)
Mogamulizumab + Total Skin Electron Beam Therapy (TSEB)
Treatment with mogamulizumab will be continued until disease progression or the occurrence of another withdrawal criterion as specified in the protocol.
TSEB will start 28 days after mogamulizumab cycle 2 day 1 at a dose of 12 Gy in 8 fractions over two weeks (4 fractions per week).
干预措施: Total Skin Electron Beam Therapy (TSEB) (Radiation)
Mogamulizumab + Total Skin Electron Beam Therapy (TSEB)
Treatment with mogamulizumab will be continued until disease progression or the occurrence of another withdrawal criterion as specified in the protocol.
TSEB will start 28 days after mogamulizumab cycle 2 day 1 at a dose of 12 Gy in 8 fractions over two weeks (4 fractions per week).
干预措施: Mogamulizumab (subsequent cycles post TSEB) (Drug)
结局指标
主要结局
Progression Free Survival Rate at 48 weeks
时间窗: Up to 48 weeks after start of mogamulizumab for each patient
The primary endpoint is the progression free survival rate, assessed at 48 weeks after start of mogamulizumab
次要结局
- Occurrence of Adverse Events(48 months after last patient in)
- Response rate to both mogamulizumab and TSEB(From the first patient treatment start till 48 weeks as of last patient in)
- Progression-free survival(From the first patient treatment start till 48 weeks as of last patient in)
- Duration of response(From the first patient treatment start till 48 weeks as of last patient in)
- Time to next treatment(From the first patient treatment start till 48 weeks as of last patient in)
- Overall survival(From the first patient treatment start till 5 years after last patient treatment)
- Time to progression(From the first patient treatment start till 48 weeks as of last patient in)