Phase 1 Study of Recombinant Human IL-15 (rhIL-15) and Mogamulizumab for Patients With Refractory or Relapsed Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin 15 (IL-15) (rhIL-15)
研究概览
简要总结
Background:
Adult T-cell leukemia/lymphoma (ATLL) and mycosis fungoides/Sezary syndrome (MF/SS) are cancers that form in the T cells, a type of white blood cell that helps with the body's immune response. A combination of drugs might be able to better treat these cancers than existing therapies.
Objective:
To test if the drugs interleukin-15 (IL-15) and mogamulizumab are safe and effective to treat people with Adult T-Cell Leukemia and Mycosis Fungoides/Sezary Syndrome (ATLL or MF/SS).
Eligibility:
People ages 18 and older with relapsed ATLL or MF/SS that has not responded to at least one standard treatment
Design:
Participants will be screened with:
Medical history
Physical exam
Blood (including human immunodeficiency virus (HIV), hepatitis B and C), urine, lung, and heart tests
Bone marrow tests (if needed): A needle inserted in the participants hip will take a small amount of marrow.
Computed tomography (CT), positron emission tomography (PET) and/or magnetic resonance imaging (MRI) scans
Tumor biopsy (if needed): A needle will take out a small piece of the participants tumor.
Participants will get the study drugs by vein for up to six 28-day cycles. They will get IL-15 the first 5 days of each cycle. They will get mogamulizumab on days 1, 8, 15, and 22 of cycle 1 and days 1 and 15 of the other cycles. They will be hospitalized for 1 week in cycle 1. They may need to get a midline catheter. This is a soft tube put into a vein leading to the heart.
Participants will have repeats of the screening tests throughout the study.
After treatment, participants will have visits every 60 days for 6 months, every 90 days for 2 years, and then every 6 months for 2 years.
详细描述
Background:
- Advanced mycosis fungoides, its leukemic form Sezary syndrome (MF/SS), and adult T- cell leukemia/lymphoma (ATLL) are all aggressive mature T-cell malignancies which are considered incurable without an allogeneic stem cell transplant.
- Mogamulizumab is a defucosylated monoclonal antibody directed towards C-C Motif Chemokine Receptor 4 (CCR4), a chemokine receptor expressed by the majority of MS/SS and ATLL cells. It is approved by the United States Food and Drug Administration for treatment of relapsed MF/SS and is recommended by the National Comprehensive Cancer Network for treatment of ATLL.
- Defucosylation of mogamulizumab is thought to enhance its capacity for antibody- dependent cell cytotoxicity (ADCC), which is mediated by natural killer (NK) cells and macrophages.
- The immunologic effects of recombinant human Interleukin-15 (rhIL-15), a stimulatory cytokine that promotes the differentiation and activation of natural killer (NK) cells, monocytes and long- term cluster of differentiation 8 (CD) 8+ memory T-cells, has been assessed in several phase I trials in cancer patients.
- Concomitant administration of rhIL-15 with mogamulizumab may further enhance the ADCC capacity of the antibody and result in improved efficacy for patients with CCR4- expressing cancers.
Objectives:
-To determine the safety and toxicity profile and the maximum tolerated dose (MTD) of continuous intravenous infusion (civ) rhIL-15 administration in combination with standard intravenous (IV) mogamulizumab treatment
Eligibility:
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1- Experimental Treatment: Dose Escalation
Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at escalating doses of 2 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kgdays 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
干预措施: Recombinant human Interleukin-15 (rhIL-15) (Drug)
1- Experimental Treatment: Dose Escalation
Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at escalating doses of 2 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kgdays 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle to determine MTD.
干预措施: Mogamulizumab (Biological)
2- Experimental Treatment: Dose Expansion
Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at the maximum tolerated dose (MTD) on days 1- 5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kgdays 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle.
干预措施: Recombinant human Interleukin-15 (rhIL-15) (Drug)
2- Experimental Treatment: Dose Expansion
Interleukin-15 (IL-15) by continuous intravenous (CIV) infusion at the maximum tolerated dose (MTD) on days 1- 5 of each 28-day cycle (max 6 cycles) with mogamulizumab by intravenous (IV) infusion at a dose of 1 mg/kgdays 1, 8, 15 and 22 of cycle 1 and days 1 and 15 of each subsequent cycle.
干预措施: Mogamulizumab (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin 15 (IL-15) (rhIL-15)
时间窗: 28 days
The MTD is the dose level at which no more than 1 of up to 6 patients experience DLT during the DLT evaluation window(s), or the dose below that at which at least 2 (of ≤6) patients have DLT. A dose-limiting toxicity (DLT) is defined as: any grade 3, 4, or 5 toxicity if not incontrovertibly due to disease progression or an extraneous cause, and deemed possibly, probably or definitely related to IL-15 or mogamulizumab.
Number of Grade 1-4 Treatment Related Adverse Events
时间窗: Date treatment consent signed to date off study, approximately 5 months and 25 days for dose level 1, and 4 months and 14 days for dose level 2.
Adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. And Grade 5 is death related to adverse event.
次要结局
- Progression-free Survival(Up to one year)
- Event Free Survival(Up to one year)
- Number of Participants Overall Response(6 cycles (one cycle is 28 days))
研究者
Kevin Conlon, MD
Principal Investigator
National Cancer Institute (NCI)