A Pilot Study of Pembrolizumab in Combination With Decitabine and Hypofractionated Index Lesion Radiation in Pediatric and Young Adult Patients With Relapsed and Refractory Solid Tumors or Lymphoma
概览
- 阶段
- 早期 1 期
- 干预措施
- Pembrolizumab
- 疾病 / 适应症
- Childhood Solid Tumor
- 发起方
- Children's Hospital Medical Center, Cincinnati
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Feasibility of administering Pembrolizumab in combination with Decitabine and hypofractionated index radiation
- 状态
- 已完成
- 最后更新
- 2个月前
概览
简要总结
This pilot study is designed to assess the safety, tolerability, and preliminary anti-tumor activity of the combination of pembrolizumab, decitabine and fixed-dose hypofractionated index site radiotherapy in pediatric and young adult patients with relapsed, refractory or progressive non-primary CNS solid tumors and lymphomas.
Primary Objectives
- To determine the feasibility of administering pembrolizumab in combination with decitabine and hypofractionated index lesion radiation
- To identify the treatment related toxicity and tolerability of the combination of decitabine and pembrolizumab with hypofractionated index lesion radiation
Secondary Objective
To preliminarily define the anti-tumor efficacy of the combination of pembrolizumab, decitabine and hypofractionated index lesion radiation in patients with relapsed, refractory, or progressive non-CNS solid tumors and lymphomas using overall response rate (CR + PR) by irRECIST after 2 cycles of therapy.
Exploratory Objectives
To profile the kinetics of the immune response and to correlate with promotor methylation changes, nuclear imaging, stool microbiota diversity, and tumor associated antigen immune responses.
详细描述
Patients will receive pembrolizumab and decitabine every 28 days, and a single 3 day course of fixed-dose hypofractionated index site radiotherapy to one or more index lesions. One cycle lasts 28 days. Radiation is given in Cycle 1 only. Cycles may repeat for a total of 26 cycles if patient meets criteria to continue protocol therapy.
研究者
入排标准
入选标准
- •Criteria: Inclusion Criteria:
- •Age: greater than or equal to 12 months and less than or equal to 40 years.
- •Diagnosis: Patients must have had histologic verification of malignancy at original diagnosis or relapse. Eligible diagnoses include:
- •Relapsed or refractory solid tumors (excluding primary CNS tumors)
- •Lymphoma in second or greater relapse or with refractory disease
- •Disease Evaluation: Patients must have evaluable or measurable disease (patients with evaluable disease must have at least one lesion that is amenable to radiation as below).
- •Patients with stable non-brainstem CNS metastases may be eligible.
- •Therapeutic Options: Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life.
- •Performance Level: Lansky/Karnofsky greater than or equal to
- •Prior Therapy: Patients who have previously received inhibitors of PD-1, PD-L1, CTLA4 or other immune checkpoint inhibitors, regardless of response, are eligible as long as they had not experienced a medically significant immune related adverse event that required treatment with supraphysiologic steroids or other immunomodulatory drug.
排除标准
- •Patients with primary CNS tumors, brainstem metastases, and/or carcinomatous meningitis are not eligible.
- •Pregnant or breast-feeding women will not be entered on this study.
- •Corticosteroids and other immunosuppressive therapy: Patients requiring systemic corticosteroids or other immunosuppressive medication within 7 days prior to enrollment are not eligible with the exception of physiologic replacement doses of corticosteroids.
- •Patients who are currently receiving another investigational drug are not eligible.
- •Patients who are currently receiving other anti-cancer agents are not eligible.
- •Patients with a history of a non-thyroiditis autoimmune disorder are not eligible. Asymptomatic laboratory abnormalities (e.g. ANA, rheumatoid factor) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder. Autoimmune thyroiditis will not render a patient ineligible.
- •Patients with known hepatitis B (HBsAg reactive) or C (HCV RNA -qualitative is detected) are excluded.
- •Patients with HIV are excluded if they have detectable viral loads or CD4 count is below 400 or they are not compliant with antiretroviral agents.
- •Patients who have an uncontrolled infection are not eligible.
- •Patients with immunodeficiency syndromes are not eligible.
研究组 & 干预措施
Pembrolizumab, Decitabine, Radiation
Patients will receive pembrolizumab and decitabine every 28 days, and a single 3 day course of fixed-dose hypofractionated radiotherapy to one or more index lesions.
干预措施: Pembrolizumab
Pembrolizumab, Decitabine, Radiation
Patients will receive pembrolizumab and decitabine every 28 days, and a single 3 day course of fixed-dose hypofractionated radiotherapy to one or more index lesions.
干预措施: Decitabine
Pembrolizumab, Decitabine, Radiation
Patients will receive pembrolizumab and decitabine every 28 days, and a single 3 day course of fixed-dose hypofractionated radiotherapy to one or more index lesions.
干预措施: Hypofractionated Index Site Radiation
结局指标
主要结局
Feasibility of administering Pembrolizumab in combination with Decitabine and hypofractionated index radiation
时间窗: Days 1 thru 57
Incidence of number of patients who experience a DLT
次要结局
- Define anti-tumor efficacy of treatment combination of pembrolizumab, decitabine, and hypofractionated index radiation (per irRECIST criteria)(2 cycles (56 days))
- Identification of treatment related toxicities and tolerability(Days 1 thru 57)