A Phase 1 Single Center Safety and Feasibility Study of Primary T Regulatory Cell Therapy to Treat Visceral Acute Graft-versus-Host Disease Following Hematopoietic Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 2
- 主要终点
- Incidence of grade 3 infusion reaction within 24 hours of infusion
研究概览
简要总结
This phase I trial studies the side effects and best dose of donor regulatory T cells in treating patients with graft-versus-host disease affecting the liver or gastrointestinal organs (visceral) within 100 days (acute) after undergoing a stem cell transplant. Graft-versus-host disease occurs when donor immune cells infused in a stem cell transplant attack the gut, skin, liver, or other organ systems of the patient. Regulatory T cells are a type of immune cell that may be able to reduce the attack of the donor's immune cells on the patient's normal cells and help treat graft-vs-host disease.
详细描述
PRIMARY OBJECTIVES:
I. Determine the safety and feasibility of donor T regulatory (Treg) cell infusions in subjects with visceral acute graft-versus-host disease (aGVHD) and incidence of dose limiting toxicities (DLTs) graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4 [v.4]) with a focus on infusion reactions within 24 hours, respiratory distress within 72 hours of infusion and all-cause mortality within 28 days of infusion.
SECONDARY OBJECTIVES:
I. Determine the quantitative blood Treg cell changes following the cell infusions.
II. Assess dosing requirements and treatment response rates to primary steroid, secondary and tertiary immunosuppressive therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Visceral aGVHD defined as: at least stage III/IV acute liver or stage II/III gastrointestinal (GI) GVHD by clinical criteria and/or GI and/or liver biopsy confirmation showing no alternative explanation for symptoms of GVHD
- •Ability to understand and willingness to sign a written informed consent form
- •Must have a 7/8 or 8/8 or haploidentical related donor matched at the human leukocyte antigen (HLA)-A, B, C, DRB1 who was evaluated and provided the donor transplant graft
- •Myeloablative or non-myeloablative allogeneic hematopoietic cell transplantation
- •Karnofsky performance status >= 50
- •DONOR: Age >= 18 to =< 77 years old
- •DONOR: Karnofsky performance status of >= 70% defined by institutional standards
- •DONOR: Must be the same sibling donor from whom the recipient's blood and marrow graft was collected for the original allogeneic transplant that is HLA 7/8 or 8/8 or haploidentical matched at the HLA-A, B, C, and DRB1
- •DONOR: Serologies for human immunodeficiency virus (HIV) antigen (Ag), HIV 1 and HIV 2 antibody (Ab), human T-cell lymphotropic virus (HTLV) 1 and HTLV 2 Ab, hepatitis B surface antigen (sAg) or polymerase chain reaction (PCR)+, or hepatitis C Ab or PCR+, syphilis (Treponema) screen and HIV 1 and hepatitis C by NAT (nucleic acid testing) have been collected prior to apheresis
- •DONOR: Female donors of child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within two weeks of apheresis
- •DONOR: Capable of undergoing leukapheresis, have adequate venous access, and be willing to undergo insertion of a central catheter should leukapheresis via peripheral vein be inadequate
- •DONOR: Donor selection will be in compliance with 21 Code of Federal Regulations (CFR) 1271
排除标准
- •Uncontrolled infections not responsive to antimicrobial therapy requiring intensive critical care
- •Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
- •Cytomegalovirus colitis or enteritis as defined by cytomegalovirus (CMV) shell vial or culture positivity from endoscopic biopsy the discretion of the treating physician based upon PCR positivity, clinical presentation and histology
- •Respiratory insufficiency with oxygen requirement > 4 L nasal cannula
- •Multi-organ failure
- •DONOR: Evidence of active infection or viral hepatitis
- •DONOR: HIV positive
- •DONOR: Pregnant donor
- •DONOR: Factors which place the donor at increased risk for complications from leukapheresis
结局指标
主要结局
Incidence of grade 3 infusion reaction within 24 hours of infusion
时间窗: 24 hours
Dose-limiting toxicity will be defined as CTCAE Grade 3 or higher cytokine/release syndrome/acute infusion reaction within 24 hours after Treg cell infusion. The rates of defined DLTs will be calculated and the one-sided upper 80%, 90%, and 95% confidence limits calculated.
次要结局
- Incidence of grade 3 or higher non-GVHD infusion-related adverse events(Up to day 28)
- Grade 4 (life threatening) respiratory distress(72 hours)
- Overall survival (OS)(Day 100)
- Incidence of cGVHD.(180 days)
- Grade 4 (life threatening) or 5 (fatal) adverse events(28 days)
- Change in blood Treg cell numbers following the infusions(Baseline to up to day 28)
研究者
Everett Meyer
Assistant Professor of Medicine
Stanford University