A Phase 2 Study of Ex Vivo TCR αβ T Cell Depletion for Graft-Versus-Host Disease (GVHD) Prophylaxis in Mismatched Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Number of Participants With Severe Acute GVHD-free Survival
研究概览
简要总结
This research study is studying the removal of a subset of white blood cells (called alpha/beta T cells) from the donor product using a cell separation device before the product is transplanted into the participant.
The device used to remove the α/βT cells in this study is:
-CliniMACS® TCR α/β Reagent System
详细描述
Patients who receive an allogeneic (using another person as the donor) stem cell transplant (SCT) are at risk for developing graft-versus-host disease (GVHD).
The word "graft" refers to the donor blood cells that you will receive during the transplant. The word "host" refers to the person receiving the cells. GVHD is a complication of transplantation where the donor graft attacks and damages some of the participant's tissues.
GVHD may occur when the T cells (a type of white blood cell that helps protect the body from infection) from the donor react against normal tissues or organs in the body. There are two basic types of GVHD:
- Acute GVHD often occurs early (generally first 3-6 months after SCT) may affect skin, gastrointestinal tract (stomach and intestines) and liver.
- Chronic GVHD often occurs later (Usually after 3-6 months after SCT) and may affect many organs and significantly diminish quality of life.
To confirm the diagnosis of acute or chronic GVHD, the participant may be asked to have a biopsy (a small sample of the participant's tissue to look at under the microscope) of the skin, gut, or, rarely, the liver.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnoses and stage at time of transplant admission:
- •Acute leukemia (AML or ALL or MPAL) in first or subsequent remission
- •Myelodysplastic syndromes (MDS) with <10% marrow blasts
- •Myeloproliferative neoplasm (MPN) with <10% marrow blasts
- •CMML with less than 10% marrow blast
- •CML accelerated phase or second or subsequent chronic phase
- •Non-Hodgkin's lymphoma in PR or CR2 or beyond
- •Hodgkin lymphoma in PR or CR2 or beyond
- •Age 18-65 years
- •Patient has a related or unrelated donor who is 8 or 9 out of 10 match at HLA A, B, C, DRB1 and DQB1, based on allele level typing.
- •Patient ECOG performance status 0-2 (Karnofsky ≥60%, see Appendix A)
- •Patient deemed to be appropriate candidate for myeloablative conditioning transplantation.
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Patient with active HIV infection
- •Chronic active hepatitis B infection (HepB surface Ag+ or detectable Hep B viral load)
- •Prior allogeneic hematopoietic stem cell transplantation
- •Impaired cardiac function- ejection fraction < 40%
- •Impaired pulmonary function- pretransplant FEV1, DLCO < 50%
- •Impaired renal function, based on
- •-Serum creatinine > 2.0 mg/dl
- •Impaired liver function unrelated to primary disease, based on
- •-ALT or AST > 3x ULN, or Total Bilirubin > 2.0mg/dl (with exception for known or suspected Gilbert's disease)
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Women who are pregnant or breast feeding. Women of child bearing potential must have a negative serum pregnancy test at study entry.
- •Participants who are receiving any other investigational agents are eligible but such agent must be discontinued before admission for HSCT, and if resumption of investigation agent is planned after HSCT, this must be approved by the study PI.
- •Participants with known active CNS disease. CNS disease that has been treated is eligible
结局指标
主要结局
Number of Participants With Severe Acute GVHD-free Survival
时间窗: 100 Days
Number of participants with severe acute GVHD-free survival will be assessed at 100 days post-SCT
次要结局
- Number of Participants With GVHD and Relapse Free Survival (GRFS)(2 years)
- Number of Participants With Immunosuppression-free Survival(2 years)
- Number of Participants With Immune Reconstitution(2 years)
- Number of Participants With Relapse-free and Overall Survival(2 years)
- Number of Participants With Grades II-IV Acute GVHD(2 years)
- Number of Participants With Hematologic Recovery(2 years)
- Number of Participants With Chronic GVHD(2 years)
- Number of Participants With Disease Relapse(2 years)
- Number of Participants With Transplant-related Mortality(2 years)
- Number of Participants With Organ Toxicity(2 years)
- Rates of Infections(2 years)
研究者
Vincent T. Ho, MD
Principal Investigator
Dana-Farber Cancer Institute