A Phase I Study: Low-Dose Total Lymphoid Irradiation in the Treatment of Refractory Chronic Graft Versus Host Disease
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Incidence of Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0
研究概览
简要总结
This phase I trial studies the side effects and best dose of low-dose total lymphoid irradiation (LD-TLI) in treating patients with chronic graft-versus-host disease that has not responded to treatment with steroids. LD-TLI is a procedure in which all of the body's major lymph nodes are treated with small doses of radiation in order to reset the dysfunctional immune system. LD-TLI may work as a treatment for graft-versus-host disease caused by a bone marrow or stem cell transplant.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety of total lymphoid irradiation (TLI) in cohorts of a selected population of refractory chronic graft-versus-host disease (GvHD) patients, given to cohorts with a total cumulative doses of TLI of 100, 150, 200, 250 or 300 centigray (cGy).
SECONDARY OBJECTIVES:
I. To evaluate the efficacy (failure free survival [FFS] at 6 months) of this therapy in the study population.
II. Approximate the efficacy at different dose levels using the GvHD summary scores.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 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
- •Patients may have received a prior allogeneic hematopoietic stem cell transplant (alloHSCT) for any indication and from any donor
- •Patients must have a diagnosis of cGvHD, in accordance with National Institutes of Health (NIH) guidelines; patients with "overlap syndrome" are also eligible; NOTE: Patients with recurrent, late onset and/or persistent acute GvHD (alone) are not eligible
- •Patients with chronic GvHD who have been exposed to two or more lines of therapy, including at least one of which was composed of a glucocorticoid and a calcineurin inhibitor are eligible.
- •Patients must have active, but not rapidly progressive, refractory cGvHD; any degree of severity (as per NIH criteria) and/or pattern of organ involvement may be considered; that said, patients with more severe and/or extensive chronic GvHD are expected to be the usual candidates for therapy
- •As above, GvHD should be controlled to a degree that would potentially allow no additional requirement for systemic IST before and following TLI =< -15 and >= day (d) +45, respectively
- •The ability to administer protocol doses of TLI (i.e., 100, 200 or 300 cGy) without exceeding cumulative doses of radiation must be established; for patients with prior radiotherapy exposure, this determination will be made by Dr. Greven (or her designee) using published guidelines for excessive organ exposure
- •Karnofsky performance status (KPS) >= 60%
- •White blood cells >= 3,000/mcL
- •Absolute neutrophil count >= 1,500/mcL
- •Hemoglobin >= 10.0 g/dL
- •Platelets >= 100,000/mcL
- •NOTE: If such hematologic abnormalities are present and deemed due to the process of cGvHD, such requirements may be waived with the approval of the PI
- •Patients must have non-hematologic organ function as defined below:
- •Left ventricular ejection fraction (LVEF) > 40%
- •Key pulmonary function tests (PFTs) > 40%
- •No further criteria for non-hematologic organ function are specified; however, if moderate-to-severe (major) organ function is present, such should be discussed with the PI, as various degrees of non-hematologic organ dysfunction may compromise either (or both) outcomes and toxicity evaluation
- •If there is concern regarding potential reversibility of any specific organ dysfunction, this issue should be addressed by consultation with an appropriate sub-specialist
- •Ability to understand and the willingness to sign an institutional review board (IRB)-approved informed consent document
排除标准
- •Patients with evidence of persistent or active malignancy or uncontrolled infection at the time of study entry
- •Patients who are pregnant or breastfeeding
研究组 & 干预措施
Supportive Care (TLI)
Patients undergo LD-TLI daily for 1-2 days.
干预措施: laboratory biomarker analysis (Other)
Supportive Care (TLI)
Patients undergo LD-TLI daily for 1-2 days.
干预措施: questionnaire administration (Other)
Supportive Care (TLI)
Patients undergo LD-TLI daily for 1-2 days.
干预措施: total nodal irradiation (Radiation)
结局指标
主要结局
Incidence of Adverse Events, Scored as Per Common Toxicity Criteria Version 4.0
时间窗: At day 180
Toxicities (grade 2 and higher) will be reported as number of occurrences.
Failure Free Survival (FFS) as Assessed by Scoring for Chronic GvHD - Specific Core Measures
时间窗: Time from baseline to date of last follow-up or failure event, assessed at day 180
Estimated along with 95% confidence intervals (CI). Descriptive statistics will be calculated and presented for GvHD summary scores by dose level and visit.
次要结局
- Immunomodulatory/Immuno-suppressive Effects(Up to 1 year)