Multi-Center, Open-Label, Randomized Study of Anti-CCR4 Monoclonal Antibody KW-0761 or Investigator's Choice in Subjects With Previously Treated Adult T-cell Leukemia-Lymphoma (ATL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 71
- 试验地点
- 20
- 主要终点
- Overall Response Rate
研究概览
简要总结
The purpose of this study is to estimate the overall response rate of subjects with relapsed or refractory Adult T-cell Leukemia-Lymphoma (ATL).
详细描述
CCR4 expression in ATL patients has been demonstrated to be very high and has been associated with shorter survival compared with CCR4-negative patients. KW-0761, a monoclonal antibody targeted to CCR4, has been shown to be safe and tolerable in several clinical trials in subjects with a variety of T-cell malignancies, including ATL, mycosis fungoides and Sézary syndrome. The objective of this study is to estimate the overall response rate of KW-0761 for subjects with relapsed or refractory ATL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Males and female subjects ≥ 18 years of age
- •Confirmed diagnosis of ATL (excluding smoldering subtype)
- •Subjects must currently have evidence of disease in at least one of the following:
- •Lymph nodes
- •Extranodal masses
- •Spleen or liver
- •Peripheral blood
- •Bone marrow
- •Relapsed or refractory after at least one prior systemic therapy regimen for ATL;
- •Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry
- •Resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE, v.4.0)
- •Adequate hematological, hepatic and renal function
排除标准
- •Smoldering subtype of ATL;
- •Lymphomatous or acute subtype subject with > 2 prior systemic therapy regimens and who has not achieved a response (CR or PR) or maintained stable disease for at least 12 weeks on last immediate prior therapy;
- •History of allogeneic transplant;
- •Autologous hematopoietic stem cell transplant within 90 days of study entry;
- •Untreated human immunodeficiency virus (HIV)
- •Has known hepatitis C. Patients who are hepatitis C antibody positive but are hepatitis C quantitative PCR negative may be enrolled;
- •Has hepatitis B based on PCR testing for hepatitis B virus DNA. Patients who are hepatitis B core antibody positive but PCR negative may be enrolled if placed on appropriate anti-hepatitis B virus prophylaxis prior to commencing treatment with KW-
- •Patients who are hepatitis B core antibody positive based on prior vaccination need not receive prophylaxis;
- •Have had a malignancy in the past two years except non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current PSA < 0.1 µg/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular carcinoma in situ of the breast who is currently without evidence of disease;
- •Clinical evidence of central nervous system (CNS) involvement or metastasis. In subjects suspected of having CNS disease, an MRI of the brain and/or lumbar puncture should be done to confirm;
- •Psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit compliance with study requirements;
- •Significant uncontrolled intercurrent illness
- •Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;
- •Known active autoimmune diseases will be excluded (For example; Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);
- •Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
- •Prior treatment with KW-0761;
- •Initiation of treatment with systemic corticosteroids while on study is only permitted for acute and brief complications of underlying disease (e.g., hypercalcemia) or for treatment related side effects (e.g., including pre-medication for infusion reaction, nausea and vomiting). Subjects on systemic corticosteroids prior to enrollment must be off for 7 days before initiation of study treatment, unless specifically indicated for the treatment of hypercalcemia. (subjects may receive inhalation corticosteroids and replacement doses of systemic corticosteroids as needed);
- •Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to Pre-treatment Visit may continue use at the same dose, although the investigator should attempt to taper the use to lowest dose tolerable;
- •Have had interferon-α and/or zidovudine within 1 week, or anti-neoplastic chemotherapy, radiation, immunotherapy, or investigational medications within 2 weeks of first study treatment;
- •Subjects on any immunomodulatory drug. Subjects on any immunomodulatory drug within 4 weeks of their first dose of KW-0761 are also excluded.
研究组 & 干预措施
KW-0761
anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab)
干预措施: KW-0761 (Biological)
investigator's choice
Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP
干预措施: Pralatrexate (Drug)
investigator's choice
Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP
干预措施: gemcitabine plus oxaliplatin (Drug)
investigator's choice
Comparator is investigator's choice of pralatrexate or gemcitabine plus oxaliplatin or DHAP
干预措施: DHAP (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first
Overall Response Rate was determined based on the response in all compartments (lymph nodes, extranodal masses, spleen/liver, skin, peripheral blood, and bone marrow), referencing Tsukasaki, 2009 as follows: Complete Response (CR) = All compartments involved with disease must be CR; Uncertified Complete Response (CRu) = \> 75% decrease in lymph nodes and/or extranodal disease with all other compartments involved with disease CR; Partial Response (PR) = If any compartment is CR/PR and all other compartments involved with disease are at least SD; Stable Disease (SD) = All compartments involved with disease are SD; Progressive Disease (PD) = PD in any compartment. Lymph node and extranodal masses response ≥50% decrease by CT, skin response ≥50% decrease in mSWAT score; blood response ≥50% decrease in malignant cells by flow cytometry; normal bone marrow if abnormal at baseline. PD equals New or ≥50% increase in any compartment.
次要结局
- Progression Free Survival(From date of randomization until the date of first documented progression, start of alternative therapy, or date of death from any cause, whichever came first, up to 36 months)
- Overall Survival(up to 36 months)
- Change in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Total Score(From date of randomization until the date of first documented progression, up to 36 months)