NCT03683498已完成1 期
A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in Patients Who do Not Obtain Complete Remission With Ruxolitinib
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla1 个研究点 分布在 1 个国家目标入组 16 人开始时间: 2018年9月25日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Toxicity and maximum tolerated dose
研究概览
简要总结
A Phase I Trial of Donor Regulatory T-cells for Steroid-Refractory Chronic Graft-versus-Host-Disease in patients who do not obtain complete remission with ruxolitinib
详细描述
The study design is based on a phase I trial in Spanish.
A number of 16 patients will be included to assess the safety and maximum tolerated dose-level of donor regulatory enriched T cell (Treg) in steroid-refractory chronic graft versus host disease (cGVHD) patients who did not obtain complete remission under treatment with ruxolitinib.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Recipient of allogeneic hematopoietic stem cell transplantation.
- •Participants must have steroid-refractory cGVHD and had obtained a partial response after at least 4 weeks of treatment with ruxolitinib.
- •Steroid-refractory cGVHD is defined as having persistent signs and symptoms of cGVHD (Appendix D) despite the use of prednisone at ≥0.25 mg/kg/day (or 0.5 mg/kg every other day) for at least 4 weeks (or equivalent dosing of alternate glucocorticoids) without complete resolution of signs and symptoms.
- •Stable dose of glucocorticoids for 4 weeks prior to enrolment
- •No addition or subtraction of other immunosuppressive medications (e.g., calcineurin-inhibitors, sirolimus, mycophenolate-mofetil) for 4weeks prior to enrolment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug
- •No age limit. In the case of children participating in the study, the informed consent will be signed by a parents or legal guardians
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Participants must have adequate organ function
- •Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Ongoing prednisone requirement >1 mg/kg/day (or equivalent).
- •Concurrent use of calcineurin-inhibitor plus sirolimus (either agent alone is acceptable).
- •History of thrombotic microangiopathy, hemolytic-uremic syndrome or thrombotic thrombocytopenic purpura.
- •New immunosuppressive medication in the 4 weeks prior.
- •Extra-corporeal Photopheresis or rituximab therapy in the 4 weeks prior.
- •Post-transplant exposure to T-cell or Interleukin-2 targeted medication (e.g. alemtuzumab, basiliximab, denileukin diftitox) within 100 days prior.
- •Donor lymphocyte infusion within 100 days prior.
- •Active malignant relapse.
- •Active uncontrolled infection.
- •Organ transplant (allograft) recipient.
- •HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with the agents used after allogeneic hematopoietic stem cell transplant (HSCT). In addition, these individuals are at increased risk of lethal infections. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- •Individuals with active uncontrolled hepatitis B or C are ineligible as they are at high risk of lethal treatment-related hepatotoxicity after hematopoietic stem cell transplant (HSCT).
- •Other investigational drugs within 4 weeks prior to enrolment, unless cleared by the Principal Investigator.
- •Pregnant women are excluded from this study.
研究组 & 干预措施
Regulatory T-cell enriched infusion
Experimental
Dose escalation sequential cohorts Regulatory T-cell enriched infusion (Cells/kg) will be administered. The cohorts will be dose escalated per the schema below:
Dose-level A: 0.5 x 10ˆ6 Cells/kg Dose-level B: 1 x 10ˆ6 cell/kg Dose-level C: 2 x 10ˆ6 cell/kg
干预措施: Regulatory T-cell enriched infusion (Biological)
结局指标
主要结局
Toxicity and maximum tolerated dose
时间窗: Up 12 weeks after infusion
To determine the maximum tolerated dose (MTD) and toxicity of Treg-enriched infusion among patients receiving ruxolitinib.
次要结局
- Immunologic effects through phenotypical evaluation(Up 12 weeks after Treg infusion)
- Immunologic effects through immune globulins.(Up 12 weeks after Treg infusion)
- Immunologic effects through plasma banking(Up 12 weeks after Treg infusion)
- Clinical response of Treg-enriched infusion(Up 12 weeks after Treg infusion)
- Immunologic effects through additional mononuclear cells.(Up 12 weeks after Treg infusion)
- Quantification of targeted cells of manufacturing Treg-enriched product meeting the targeted cell dose-level.(Before 24 hours to infusion up infusion day)
- Survival after one year of Treg infusion(1 year after Treg infusion)
研究者
研究点 (1)
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