NCT02659800终止1 期
A Phase I and Pilot Study of the Effect of rhIL-7-hyFc (NT-I7) on CD4 Counts in Patients With High Grade Gliomas and Severe Treatment-related CD4 Lymphopenia After Concurrent Radiation and Temozolomide
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins20 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2018年10月30日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 20
- 主要终点
- Absolute total CD4 cell counts
研究概览
简要总结
The purpose of this study is to determine the maximum tolerated dose (MTD) and select optimal biological doses (OBD) of the study drug NT-I7 in High Grade Glioma patients with severe lymphopenia, as well as to test the effect of NT-I7 on the CD4 counts of patients in comparison to control participants. This study has both a Phase I and Pilot component.
详细描述
PRIMARY OBJECTIVES:
Phase I: To determine the MTD (Maximum Tolerated Dose) and select optimal biological doses (OBD) of NT-I7 in HGG patients with severe lymphopenia
Pilot Study: To test the effect of NT-I7 on CD4 counts compared to control
SECONDARY OBJECTIVES:
- To evaluate the optimal biological dose of NT-I7
- To evaluate the effect of concurrent dexamethasone
- To evaluate the duration of effect on CD4 counts (up to 6 months)
- To evaluate the total lymphocyte counts over time and serial T cell lymphocyte subtypes and the effect on T cell repertoire (up to 6 months)
- To evaluate the serial cytokine levels (up to 6 months)
- To evaluate the impact of adjuvant temozolomide on NT-I7 effects on CD4 counts
- To evaluate anti-drug antibodies
- To evaluate the pharmacokinetic profile of NT-I7 after intramuscular administration in this patient population
- To evaluate the safety and toxicity of NT-I7 in patients with high grade glioma
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Care Provider)
盲法说明
Participant is blinded and partially randomized in the Pilot study.
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
- •Patients must have histologically confirmed high grade glioma by pathology (World Health Organization [WHO] grade III and IV)
- •Patients' post-operative treatment must have included at least 80% of standard radiation and concomitant temozolomide; patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes [TIL], lymphokine-activated killer [LAK] or gene therapy), or hormonal therapy for their brain tumor; prior Gliadel wafers are allowed; glucocorticoid therapy is allowed
- •Patients must have CD4 =< 300 cells/mm^3 in the last week (7 days) of standard radiation + temozolomide treatment (58-60 Gy radiation with temozolomide 75 mg/m2 daily during radiation)
- •Absolute neutrophil count >= 1,000/mcL
- •Platelets >= 50,000/mcL (need to confirm before administering study drug)
- •Hemoglobin >= 9 g/dL
- •Total bilirubin =< institutional upper limit of normal
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- •Creatinine =< institutional upper limit of normal OR creatinine clearance >= 60 ml/min/1.73 m^2 for patients with creatinine levels above institutional normal
- •Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT) =< 1.5 x institutional upper limit of normal
- •Patients must have a Karnofsky performance status (KPS) >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
- •Patients must be able to provide written informed consent
- •Women of childbearing potential must have a negative serum pregnancy test prior to study entry; women of childbearing potential and men must agree to use two birth control methods (either two barrier methods or a barrier method plus a hormonal method) or abstinence prior to study entry and for the duration of study participation (through at least 90 days after the last study injection); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Dexamethasone dose must be provided for treatment group assignment:
- •Group A: patients not on dexamethasone or on a dose =< 0.75 mg daily (or equivalent of an alternative corticosteroid)
- •Group B: patients who require dexamethasone >= 4 mg daily (or equivalent of an alternative corticosteroid) ** Patients must have been on the group assignment dose of corticosteroids for at least 5 days prior to the dose of NT-I7; corticosteroid dose changes prior to the start of treatment are allowed as long as they do not alter patient's group assignment
- •Exclusion Criteria
- •Patients receiving any other investigational agents are ineligible
- •Patients with known hypersensitivity to NT-I7 or any component used in the vehicle/formulation are ineligible
- •Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, are ineligible
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with NT-I7
- •Patients with human immunodeficiency virus (HIV) are excluded
- •Patients with a known or screening-period-determined corrected QT (QTc) interval > 450 msec and patients who require a therapy with a drug known to prolong the QT/QTc interval, are ineligible
- •Patients with a history of or who currently have evidence of autoimmune disease (other than autoimmune thyroid disease managed with thyroid hormone replacement or vitiligo) including: myasthenia gravis, Guillain Barre syndrome, systemic lupus erythematosus, multiple sclerosis, scleroderma, ulcerative colitis, Crohn's disease, autoimmune hepatitis, Wegener's etc., are ineligible
排除标准
- 未提供
结局指标
主要结局
Absolute total CD4 cell counts
时间窗: At 6 weeks (after standard radiation and temozolomide treatment completion)
The primary treatment effect is defined as an absolute increase in CD4 counts in patients treated with glycosylated recombinant human interleukin-7 compared to the control group patients without glycosylated recombinant human interleukin-7 at week 6 after radiation treatment + temozolomide treatment.
次要结局
- Optimal dose of glycosylated recombinant human interleukin-7 determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0(4 weeks)
研究者
研究点 (20)
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