A Phase I/IIa, Open-label, Multicenter Study of the Safety and Efficacy of CHO-H01 as a Single Agent/Combined With Lenalidomide to Subjects With Refractory or Relapsed Non-Hodgkin's Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 37
- 试验地点
- 17
- 主要终点
- Number of subjects with adverse events (AE)
研究概览
简要总结
This is a 2-part study. Part 1/Phase 1 of the study will be conducted to determine the safety and tolerability of CHO-H01 in subjects with relapsed/refractory CD20+ non-Hodgkin's lymphoma. It will also determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D).
Part 2/Phase 2a will assess the anticancer activity and safety of CHO-H01 plus lenalidomide in subjects with low-grade relapsed/refractory CD20+ non-Hodgkin's lymphoma.
详细描述
Phase I FIH study includes subjects with relapsed/refractory CD20 + non-Hodgkin's lymphoma, who may benefit from treatment with CHO-H01. In Phase I of the study, the first 2 cohorts will follow a 2-step modified accelerated titration dose escalation design and subsequent cohorts will follow a standard 3+3 dose escalation design.
The investigational medicinal product, CHO-H01, will be administered via IV infusion once weekly for 4 weeks in Cycle 1 and then once only (on Day 1) in each subsequent 21-day cycle until disease progression or for up to 6 cycles (19 weeks) of treatment.
Once the MTD/RP2D has been confirmed, Phase IIa of the study will be initiated. The purpose of Phase IIa is to assess anticancer activity and safety of CHO-H01 plus lenalidomide in low-grade relapsed/refractory CD20 + non Hodgkin's lymphoma, including follicular lymphoma (Grades 1-3a), marginal zone lymphoma, and small lymphocytic lymphoma.
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
- •Life expectancy of >12 weeks.
- •Body mass index of 18 to 32 kg/m
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Phase I: Have histologically (laboratory test) confirmed CD20 + non-Hodgkin's lymphoma according to the World Health Organization's 2016 classification:
- •Low grade lymphoma: follicular lymphoma (Grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma;
- •Other lymphoma: DLBCL (NOS: to include germinal center B-cell-like [GCB] and activated B-cell-like [ABC]), follicular lymphoma Grade 3b, mantle cell lymphoma; primary mediastinal large B-cell lymphoma.
- •Phase IIa: Histologically confirmed CD20 + non-Hodgkin's lymphoma according to the World Health Organization's 2016 classification, only low grade lymphoma: follicular lymphoma (Grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma.
- •Have at least one measurable lesion that is at least 1.5 cm in its largest dimension.
- •Off treatment for 30 days from last anti-CD20 infusion until planned administration of CHO-H
- •If no original sample is available, is willing and able to provide an adequate tumor biopsy sample at Screening.
- •Have adequate cardiac function: without clinically significant and/or uncontrolled heart disease.
- •Must be sterile, or have a monogamous partner who is surgically sterile, or at least 2 years postmenopausal, or be committed to use an acceptable form of birth control for the duration of the study (male), and for the duration of the study and for 3 months following the last CHO-H01 administration (female).
排除标准
- •Must not have a history of egg allergy or allergic reactions to any component of CHO-H
- •Must not have any known or current illnesses (such as autoimmune disease, unless well controlled or resolved), infection, or other condition that could limit study compliance or interfere with assessments.
- •Subjects who have received anti-programmed death-ligand 1 (PD-L1), programmed cell death 1 (PD-1), or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) therapy.
- •Subjects who have completed an autologous stem cell transplant within 100 days prior to CHO-H01 therapy or an allogeneic stem cell transplant.
- •Subjects with known hepatitis B surface antigen (HBsAg) seropositive or known or suspected active hepatitis C infection with detectable viral load.
- •Subjects with known human immunodeficiency virus (HIV) infection
- •Subjects who have had radiation therapy, major surgical procedure or live vaccinations within 28 days prior to CHO-H01 administration.
- •Subjects with a history of type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusions of CD20 monoclonal antibodies.
- •Subjects who have received (or are receiving) systemic corticosteroids:
- •At a daily dose higher than 15 mg prednisone or equivalent within 14 days prior to the first administration of CHO-H01;
- •Topical, inhaled, nasal, and ophthalmic steroids are allowed.
- •Inadequate bone marrow, hepatic or renal function.
- •Subjects with a history of seizure disorder.
- •Subjects who are pregnant or breast feeding.
- •Subjects with any contraindications to lenalidomide (Only for phase IIa).
研究组 & 干预措施
CHO-H01+Lenalidomide
Expansion phase with lenalidomide combination.
Phase2a:
Single cohort at Recommended Phase 2 Dose (RP2D) of CHO-H01.
干预措施: CHO-H01 at RP2D (Drug)
CHO-H01+Lenalidomide
Expansion phase with lenalidomide combination.
Phase2a:
Single cohort at Recommended Phase 2 Dose (RP2D) of CHO-H01.
干预措施: Lenalidomide (Drug)
CHO-H01
Dose escalation phase
Phase 1:
Five to six cohorts of escalating dose levels of CHO-H01 from 0.5mg/kg to 12 mg/kg.
干预措施: CHO-H01 (Drug)
结局指标
主要结局
Number of subjects with adverse events (AE)
时间窗: Through study completion, approximately 16 months
To assess the safety and tolerability of CHO-H01 as a single agent in subjects with relapsed/refractory CD20 + non-Hodgkin's lymphoma and CHO-H01 plus lenalidomide in subjects with low-grade relapsed/refractory CD20 + non-Hodgkin's lymphoma.
Number of subjects with dose-limiting toxicities
时间窗: Through study completion, approximately 16 months
All AEs and toxicities are evaluated based on the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 5.0. The 5 general grades are Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life-threatening or disabling, and Grade 5: Death (outcome of AE).
Objective Response Rate
时间窗: Through study completion, approximately 16 months
Objective response rate (ORR) is the proportion of subjects with a best overall response of complete response (CR) or partial response (PR). ORR will be measured based on Modified (not using PET imaging) Lugano Revised Criteria for Response assessment.
Best overall response
时间窗: Through study completion, approximately 16 months
The best overall response (CR, PR, stable disease \[SD\], or progressive disease \[PD\]) is defined as the best response across all time points.
次要结局
- Clinical benefit rate(Through study completion, approximately 16 months)
- Serum concentration of CHO-HO1(Through study completion, approximately 16 months)
- Progression-free survival(Through study completion, approximately 16 months)
- Serum Antidrug antibody (ADA) concentration(Through study completion, approximately 16 months)
- Overall survival(Through study completion, approximately 16 months)
- Duration of response(Through study completion, approximately 16 months)
- Time to event endpoints of time to progression (TTP)(Through study completion, approximately 16 months)
- Duration of stable disease(Through study completion, approximately 16 months)