A Phase I Open-label, Multiple Dose Study of CHO-H01 Administered Intravenously as a Single Agent to Subjects With Refractory or Relapsed Follicular Lymphoma
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 24
- 主要终点
- Adverse drug reactions
研究概览
简要总结
This is a single-arm open label trial to explore the tolerability, safety, PK, PD, and anti-tumor activity of various doses and schedules of CHO-H01 administered as monotherapy in subjects with follicular lymphoma.
Groups of 6 subjects are planned for each cohort. The first 3 patients of each cohort will be evaluated to determine if it is appropriate to proceed with the additional 3 patients at that dose and schedule.
详细描述
This is a single-arm open label trial to explore the tolerability, safety, PK, PD, and anti-tumor activity of various doses and schedules of CHO-H01 administered as monotherapy in subjects with follicular lymphoma. This is not an MTD study, but an evaluation of optimum biological activity.
Groups of 6 subjects are planned for each cohort. The first 3 patients of each cohort will be evaluated to determine if it is appropriate to proceed with the additional 3 patients at that dose and schedule.
Schema 1:
1 mg/kg administered on D1 of Cycle 1 and D1 of subsequent 28 day cycles. Up to 6 cycles total are planned per subject.
Schema 2-3 Details to be determined after analysis of first 3-6 patients treated on Schema 1. Doses may be either escalated or de-escalated, or modified for Cycles 2-6 relative to Cycle 1. Schedules to be explored could include multiple doses with the first cycle: D1, D8 of 28 day cycles and D1, D8, D15 of 28 days cycles. In no case will individual doses exceed 10mg/kg.
研究设计
- 研究类型
- Interventional
- 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
- •Age > 18 years Histologically confirmed, measurable, CD20 positive Follicular B cell lymphoma with an indication for treatment for which there is no therapy of curative potential or of higher priority
- •Life expectancy of greater than 1 year
- •ECOG performance status of 0 to 1
- •Last dose of prior anti-cancer therapy must be at least 56 days (or two half-lives for proteins, whichever is greater) prior to the first administration of the study drug (to satisfy the recognized requirement of at least 5 times the terminal half-life period for most drugs currently used, including most receptor tyrosine kinase (RTK) inhibitors).
- •Acute toxicities from any prior therapy, surgery, or radiotherapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 0 or
- •Subject must be willing and able to provide fresh tumor at Screening. Subjects will be asked to provide additional needle biopsy samples on C2D8 and C4D
- •Archival tumor biopsy (i.e., tissue block or series of ≈10 slides) is requested if available, and should be provided during the Screening period.
- •Local laboratories may be used for standard laboratory assessments:
- •Adequate bone marrow function defined by: absolute neutrophil count (ANC) of ≥ 1.5 x 109/L, platelet count of ≥ 100.0 x 109/L, and hemoglobin ≥9.0 g/dL.
- •Adequate hepatic function defined by: serum total bilirubin < 2 mg/dl (unless resulting from hemolysis), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN (or ≤ 5 x ULN in subjects with liver metastases).
- •Adequate renal function assessed by: serum creatinine within normal limits, or creatinine clearance (by Cockcroft Gault formula) ≥ 50 mL/min for subjects in whom serum creatinine may not adequately reflect renal function.
- •Must have measurable disease as described in Lugano Revised Criteria for Response. This assessment is the responsibility of the investigator who may use local radiology to support this assessment.
- •Willing and able to understand and sign an informed consent form and to comply with all aspects of the protocol.
- •Willingness to use effective methods of contraception.
- •Adequate T cell immune parameters - CD4 >500/mcL, CD8 > 250/mcL
- •Bone marrow biopsy revealing adequate hematologic reserves
排除标准
- •Evidence of circulating tumor cells >500 cells/microliter of lymphocytes or equivalent
- •History of allergic reactions to any component of the study drug
- •Autoimmune disease (Exceptions: autoimmune thyroiditis)
- •Concomitant use of systemic corticosteroids
- •History of seizure disorder
- •History of Central Nervous System (CNS) metastases or seizure disorder related to the malignancy.
- •History of symptomatic congestive heart failure (CHF), unstable angina pectoris, unstable atrial fibrillation; cardiac arrhythmia
- •Non-manageable electrolyte imbalances, including hypokalemia, hypocalcemia, hypomagnesemia, and hypomagnesemia, of Grade 2 or greater (NCI-CTCAE v. 4.0)
- •Any uncontrolled intercurrent illness, infection, or other condition that could limit study compliance or interfere with assessments
- •Pregnancy or breast feeding
研究组 & 干预措施
Open label treatment
Study drug (CHO-H01) administered on Day 1 of 28 day cycles up to 6 cycles total.
干预措施: CHO-H01 (Biological)
结局指标
主要结局
Adverse drug reactions
时间窗: 28 days
Treatment-emergent adverse events and clinically significant laboratory values assessed for each subject and aggregated by type, frequency and severity by treatment cohort
Pharmacodynamic assessment of Immune cell activation
时间窗: 64 days
Gene expression of immune cell activation following treatment compared to baseline
次要结局
- Clinical response(8 weeks)
- Serum drug concentration(72 hours)