A Phase 1 Study of Interleukin-15 in Combination With Avelumab (Bavencio) in Relapsed/Refractory Mature T-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Interleukin 15
研究概览
简要总结
Background:
Some T-cell lymphomas and leukemias do not respond to standard treatment. Researchers hope to develop a treatment that works better than current treatments.
Objective:
To test if interleukin (IL-5) combined with avelumab is safe and effective for treating certain cancers.
Eligibility:
People ages 18 and older with relapsed T-cell leukemias and lymphomas for which no standard treatment exists or standard treatment has failed
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Blood, urine, heart, and lung tests
- Possible tumor biopsy
- Bone marrow biopsy: A small needle will be inserted into the hipbone to take out a small amount of marrow.
- Computed tomography (CT) or positron emission tomography (PET) scans and magnetic resonance imaging (MRI): Participants will lie in a machine that takes pictures of the body.
Participants will get the study drugs for 6 cycles of 28 days each. They will have a midline catheter inserted: A tube will be inserted into a vein in the upper chest. They will get Interleukin-15 (IL-5) as a constant infusion over the first 5 days of every cycle. They will get avelumab on days 8 and 22 of each cycle. They will be hospitalized for the first week of the first cycle.
Participants will have tests throughout the study:
- Blood and urine tests
- Another tumor biopsy if their disease gets worse
- Scans every 8 weeks
- Possible repeat MRI
- Another bone marrow biopsy at the end of treatment, if there was lymphoma in the bone marrow before treatment, and they responded to treatment everywhere else.
After they finish treatment, participants will have visits every 60 days for the first 6 months. Then visits will be every 90 days for 2 years, and then every 6 months for 2 years. Visits will include blood tests and may include scans.
详细描述
Background:
Mature T-cell cancers are a phenotypically heterogeneous group of malignancies which constitute 10-15% of all non-Hodgkin lymphomas (NHL). Patients with relapsed/refractory T cell lymphomas have limited therapeutic options, making new therapeutic approaches extremely important.
The immunologic effects of recombinant human Interleukin-15 (rhIL-15), a stimulatory cytokine that promotes the differentiation and activation of NK cells, monocytes and long-term cluster of differentiation 8 (CD8) + memory T-cells, has been assessed in several Phase 1 trials in cancer patients.
Avelumab is an anti-programmed death ligand-1 (PD-L1) fully human immunoglobulin G1 (IgG1) antibody that inhibits programmed cell death protein 1 (PD1)/PD-L1 interactions while leaving the PD1/programmed cell death ligand 2 (PD-L2) pathway intact and enhances immune activation against tumor cells. It has received United States (U.S.) Food and Drug Administration (FDA) accelerated approval for the treatment of patients with metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma.
Unlike other approved anti-PD-L1/PD1 antibodies, avelumab induces lysis of tumor cells via antibody-dependent cell-mediated cytotoxicity (ADCC), indicating an additional mechanism of action. However, avelumab has not shown ADCC against normal immune cell subsets in humans.
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 1, 2, 3 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with avelumab by intravenous (IV) infusion at a dose of 10mg/kg on Day 8 and 22 of each cycle, to determine maximum tolerated dose (MTD)
干预措施: rhIL-15 (Drug)
1- Experimental Treatment: Dose Escalation
Interleukin-15 (IL-15) by continuous intravenous (civ) infusion at escalating doses of 1, 2, 3 and 4 mcg/kg/day on days 1-5 of each 28-day cycle (max 6 cycles) with avelumab by intravenous (IV) infusion at a dose of 10mg/kg on Day 8 and 22 of each cycle, to determine maximum tolerated dose (MTD)
干预措施: Avelumab (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 cycles 1-6 with avelumab at 10mg/kg on Day 8 and 22 of each cycle
干预措施: 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 cycles 1-6 with avelumab at 10mg/kg on Day 8 and 22 of each cycle
干预措施: Avelumab (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Interleukin 15
时间窗: First 28 days of treatment
The MTD is the dose level at which no more than 1 of up to 6 participants experience a dose-limiting toxicity (DLT) during the DLT evaluation window(s), or the dose below that at which at least 2 (of ≤6) participants 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 interleukin-15 (IL-5) by the principal investigator (PI) or designee during the first 28 days of treatment. Grade 3 is severe. Grade 4 is life threatening. Grade 5 is death related to adverse event.
次要结局
- Number of Participants With Overall Best Response(6 cycles (each cycle is 28 days) - approximately 168 days)
- Mean Duration of Response (DOR)(From the time that response to therapy is first documented until progressive disease is observed or the subject is lost to follow-up or approximately 2 years.)
- Mean Overall Survival (OS)(From study opening through May 2022 when the study was completed with a maximum follow up of approximately 2 years and 11 months for any participant.)
- Mean Progression Free Survival (PFS)(From study opening through May 2022 when the study was completed with a maximum follow up of approximately 2 years and 11 months for any participant.)
- Mean Event-free Survival (EFS)(From study opening through May 2022 when the study was completed with a maximum follow up of approximately 2 years and 11 months for any participant.)
- Overall Response in Participants With Greater Than or Equal to 50% Programmed Death-ligand 1 (PD-L1) Expressing Tumor Cells(From the time the subject began protocol treatment until end of treatment, progression or start of another therapy or approximately 2 years)
研究者
Kevin Conlon, MD
Principal Investigator
National Cancer Institute (NCI)