NCT05557903Unknown1 期
Recombinant Humanized Anti-CD52 Monoclonal Antibody in the Treatment of Relapsed and Refractory NHL and Initially Treated T-PLL Phase I Clinical Study on Safety and Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy
适应症
试验速览
- 阶段
- 1 期
- 入组人数
- 71
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
研究概览
简要总结
Phase I clinical study of multicenter, single-arm, open, non-randomized evaluation of recombinant humanized anti-CD52 monoclonal antibody in the NHL and T-PLL
详细描述
Recombinant Humanized Anti-CD52 Monoclonal Antibody Injection in the Treatment of Relapsed and Refractory NHL (Including CLL/SLL, PLL, PTCL, Diffuse Large B-cell Lymphoma, Follicular Cell Lymphoma, Mantle Cell Lymphoma, and Marginal Zone Lymphoma) and Initially Treated T-PLL Phase I Clinical Study on Safety and Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For Patients With Relapsed And Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma/Lymphoblastic Leukemia (CLL/SLL/PLL) And Initial Treated t-Lymphoblastic Leukemia ( InitialTreated T-PLL)
- •Patients with CLL/SLL or PLL were confirmed by histopathological or flow immunotyping;
- •Patients with indications for treatment according to iwCLL2018 criteria and determined by the investigator;
- •Age from 18 to 70 (including boundary value), no gender limitation;
- •ECOG physical condition score 0 ~ 2;
- •Patients have measurable lesions (lymphadenopathy (maximum baseline diameter ≥1.5 cm), or hepatomegaly/splenomegaly due to CLL or PLL or peripheral tumor lymphocytes >5×10E9/L);
- •CLL/SLL patients are intolerant or resistant to previous BTK inhibitor treatment; Or newly treated patients with T-PLL; Or relapse-resistant PLL (relapse-resistant PLL is defined as disease progression following recent remission of treatment. Treatment-resistant disease was defined as failure to achieve ≥PR from the most recent treatment or disease progression within 6 months of the last treatment);
- •Laboratory test results must meet the following requirements (no blood components, short-acting cell growth factor and other drugs are allowed within 7 days prior to laboratory test; Long-acting growth factor is not allowed within the first 14 days), and laboratory test results within 7 days before screening;
- •Bone marrow function: Neutrophils ≥1×10E9/L, platelets ≥50×10E9/L, and hemoglobin ≥75g/L were observed without growth factor support treatment.
- •Liver function: AST and ALT ≤2×ULN (no liver invasion); Alanine aminotransferase or/and aspartate aminotransferase ≤5×ULN (liver aggressor). Total bilirubin ≤2×ULN;
- •Renal function: serum creatinine ≤2×ULN and creatinine clearance rate > 50mL/min;
- •Blood coagulation function: international standardized ratio (INR) ≤1.5×ULN and activated partial thrombin time (APTT) ≤1.5×ULN;
- •Life expectancy > 3 months;
- •Fertile men and women of reproductive age are willing to take effective contraceptive measures from the signing of informed consent to 6 months after the last administration of the experimental drug; Women of childbearing age must have a negative blood pregnancy test no later than 7 days before the first trial drug is administered.
- •Agreed to follow the experimental treatment plan and visit plan, voluntarily enrolled in the study, and signed written informed consent.
- •For Other Relapsed And Refractory Non-Hodgkin's Lymphoma
- •Non-hodgkin's lymphoma was confirmed by histopathology according to world Health Organization (WHO) classification of disease, and did not respond to standard treatment;
- •ECOG physical condition score 0~2;
- •Age from 18 to 70 (including boundary value), no gender limitation;
- •Life expectancy > 3 months;
- •At least one measurable lesion with a maximum diameter ≥1.5cm is present;
- •Laboratory test results must meet the following requirements (no blood components, short acting cell growth factor, albumin and other drugs are allowed to be given within 7 days before obtaining laboratory test; Long acting growth factor is not allowed in the first 14 days) :
- •Bone marrow function: Neutrophils ≥1×10E9/L, platelets ≥50×10E9/L, and hemoglobin ≥75g/L were observed without growth factor support treatment.
- •Liver function: AST and ALT ≤2×ULN (no liver invasion); Alanine aminotransferase or/and aspartate aminotransferase ≤5×ULN (liver aggressor). Total bilirubin ≤2×ULN;
- •Renal function: serum creatinine ≤2×ULN and creatinine clearance rate >50mL/min;
- •Blood coagulation function: international standardized ratio (INR) ≤1.5×ULN and activated partial thrombin time (APTT) ≤1.5×ULN;
- •Agreed to follow the experimental treatment plan and visit plan, voluntarily enrolled in the study, and signed written informed consent.
排除标准
- •For Patients With Relapsed And Refractory CLL/SLL/PLL And Initial Treated T-PLL
- •Central nervous system (CNS) or meningeal involvement or history of such involvement before enrollment;
- •Received systemic steroid hormone (dose equivalent to prednisone ≥10mg/ day) and antitumor therapy within 7 days prior to initial administration of the study drug, chemotherapy, targeted therapy, radiotherapy or antibody therapy within 4 weeks or 5 half-lives, whichever is older; Failure to recover from AE associated with prior systemic antitumor therapy to nCI General Adverse Event Term version 5.0 (CT CAE Version 5.0) grade ≤1 (except hair loss);
- •Those who had undergone major surgery, severe trauma or were expected to undergo major surgery during the study period within 4 weeks prior to the first administration of the study drug and were judged by the investigator to be unsuitable for inclusion;
- •Autoimmune cytopenia with clinical manifestations;
- •Have a history of active, known autoimmune deficiency, or other acquired, congenital immune deficiency diseases, or a history of organ transplantation;
- •There was a history of other active malignant tumors within 2 years prior to the entry of the study, except for the following cases :(1) effectively controlled cervical cancer in situ; (2) effectively controlled local basal cell carcinoma of skin; (3) Other previous malignant tumors that have been clinically cured and have no clinical signs for ≥5 years;
- •Currently has clinical significance of cardiovascular disease, activity, such as uncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure, according to the New York heart association functional class determine any 3 or 4 heart disease, or a period of 6 months before screening history of myocardial infarction, or heart left ventricular ejection fraction < 50%;
- •Had active systemic infections (bacterial, fungal, viral, etc.) within 2 weeks prior to enrollment, including infections being treated with oral or intravenous antibiotics;
- •Known patients with acute or chronic active hepatitis b (HBsAg positive and HBV DNA viral load ≥200IU/mL or ≥10E3 copy number /mL, other abnormal results will be determined by the investigator whether to add quantitative HBV DNA test or exclude); Acute or active hepatitis C (HCV antibody positive); And other acquired, congenital immunodeficiency diseases, including but not limited to HIV-infected persons; Or treponema pallidum antibody positive; Or CMV-DNA positive;
- •Patients with or clinically suspected Richter's syndrome at the time of screening;
- •Patients who received or received radiation therapy within the first 4 weeks of enrollment (except for treated bone marrow volume less than 10% and patients with evaluable lesions beyond the radiation report). Prior radioimmunotherapy within 3 months prior to initiation of the study drug;
- •Are currently participating in an interventional clinical trial treatment, or have been treated with another clinical trial drug or device within 4 weeks prior to initial administration;
- •Received any live virus vaccine or attenuated live vaccine within 3 months prior to enrollment;
- •Prior allogeneic stem cell transplantation or autologous hematopoietic stem cell transplantation or any active graft-versus-host disease basis or immunosuppressant use within 21 days prior to initiation of investigational therapy;
- •Known history of allergic diseases or severe allergies; Or is known to be allergic to protein preparations, biological agents, or any component of the test drug;
- •Those who have a history of drug abuse or drug abuse after inquiry;
- •Pregnant or lactating women;
- •The investigator considered that the patient had other conditions that might affect compliance or ineligibility for the study.
- •For Other Relapsed And Refractory Non-Hodgkin's Lymphoma
- •Highly aggressive lymphoma of indolent lymphoma transformation;
- •Known patients with acute or chronic active hepatitis b (HBsAg positive and HBV DNA viral load ≥200IU/mL or ≥10E3 copy number /mL, other abnormal results will be determined by the investigator whether to add quantitative HBV DNA test or exclude); Acute or active hepatitis C (HCV antibody positive); And other acquired, congenital immunodeficiency diseases, including but not limited to hiv-infected persons; Or treponema pallidum antibody positive; Or cmV-DNA positive;
- •Received any anti-tumor therapy (including radiotherapy, chemotherapy, hormone therapy [dose equivalent to prednisone ≥10mg/ day], surgery or targeted therapy, immunotherapy, etc.) within 4 weeks or 5 half-life periods (whichever is longer) prior to the start of the study drug; Recovery from AE associated with prior systemic antitumor therapy to NCI General Adverse Event Term version 5.0 (CT CAE Version 5.0) grade ≤1 (except hair loss);
- •Clinically significant heart disease, including unstable angina, acute myocardial infarction 6 months prior to randomization, congestive heart failure (NYHA) heart function grade III or IV; Or left ventricular ejection fraction < 50%;
- •Lymphoma patients with central nervous system (CNS) invasion before enrollment;
- •Known history of prior drug allergy; Or is known to be allergic to protein preparations, biological agents, or any component of the test drug;
- •Those who had undergone major surgery or severe trauma within 4 weeks prior to treatment and were judged by the investigator to be unfit for inclusion;
- •Had received autologous or allogeneic hematopoietic stem cell transplantation before enrollment;
- •There was a history of other active malignant tumors within 2 years before entering the study, except for the following cases :(1) effectively controlled cervical cancer in situ; (2) effectively controlled local basal cell carcinoma of skin; (3) Other malignant tumors that have been clinically cured and have no clinical signs for ≥5 years;
- •Had an active systemic infection (bacterial, fungal, viral, etc.) within 2 weeks prior to enrollment, including an infection being treated with oral or intravenous antibiotics;
- •Participants in other clinical trials within 4 weeks prior to enrollment;
- •Received any live virus vaccine or attenuated live vaccine within 3 months prior to enrollment;
- •Autoimmune cytopenia with clinical manifestations;
- •A history of drug abuse or drug abuse upon inquiry;
- •Pregnant or lactating women;
- •The investigator considered that the patient had other conditions that might affect compliance or ineligibility for the study.
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0
时间窗: 6 weeks
Adverse events that occurred during the entire study period were evaluated and graded according to NCI-CTCAE v5.0, and dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) were observed. Safety evaluation indexes include vital signs, physical examination, 12-lead electrocardiogram, echocardiography, clinical laboratory examination indexes (blood routine, blood biochemistry, urine routine, coagulation function, etc.), changes of ECOG physical fitness score, adverse events and serious adverse event, etc.
次要结局
- Immunogenicity evaluation of anti-CD52 monoclone antibody(16 weeks)
- Efficacy evaluation of anti-CD52 monoclone antibody(16 weeks)
- Pharmacokinetic (PK) evaluation of anti-CD52 monoclone antibody（Multiple administration）(11 weeks)
- Pharmacokinetic (PK) evaluation of anti-CD52 monoclone antibody（single administration）(1 weeks)
研究者
研究点 (1)
Loading locations...
相似试验
已完成
2 期
A Trial of BTT1023 in Patients With Primary Sclerosing CholangitisPrimary Sclerosing CholangitisNCT02239211University of Birmingham23
撤回
2 期
A Safety and Efficacy Study of Human Monoclonal Antibodies, BRII-196 and BRII-198 for the Treatment of Patients With COVID-19COVID-19NCT04770467Brii Biosciences, Inc.
已完成
不适用
Alemtuzumab, MabCampath® with 2-weekly CHOP chemotherapy for mature T-cell non-Hodgkin's lymphomaMature T-cell non-Hodgkin's lymphomaCancerOther and unspecified types of non-Hodgkin's lymphomaISRCTN52265296Dutch Haemato-Oncology Association (Stichting Hemato-Oncologie Volwassenen Nederland) (HOVON) (Netherlands)20
已完成
3 期
A Phase III Study for 601 Versus Ranibizumab in Patients With Vision LossBranch Retinal Vein OcclusionNCT05520177Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.351
已完成
1 期
A Clinical Trial of Antibody GSK1070806 in the Treatment of Patients With Moderate to Severe Crohn's DiseaseCrohn DiseaseNCT03681067University of Birmingham5