CD45A-Depleted Haploidentical Hematopoietic Progenitor Cell and Natural Killer Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Percentage of Participants Engrafted by Day 42 Post-transplant
研究概览
简要总结
This pilot phase II trial studies how well a new reduced intensity conditioning regimen that includes haploidentical donor NK cells followed by the infusion of selectively T-cell depleted progenitor cell grafts work in treating younger patients with hematologic malignancies that have returned after or did not respond to treatment with a prior transplant. Giving chemotherapy and natural killer cells before a donor progenitor cell transplant may help stop the growth of cells in the bone marrow, including normal blood-forming cells (progenitor cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy progenitor cells from a related donor are infused into the patient they make red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Removing specific T cells from the donor cells before the transplant may prevent this.
详细描述
PRIMARY OBJECTIVE:
- To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical natural killer (NK) cells.
SECONDARY OBJECTIVES:
- Estimate the incidence of malignant relapse, event-free survival, and overall survival at one-year post-transplantation.
- Estimate incidence and severity of acute and chronic (GvHD).
- Estimate the rate of transplant related mortality (TRM) in the first 100 days after transplantation.
Blood progenitor cells will be collected from adult donors to be used for transplantation. Donor cells will be processed and filtered in a laboratory at St. Jude using a machine called the CliniMACS™ device, and later infused (transplanted) into the participant through his/her veins.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age less than or equal to 21 years.
- •One of the following hematologic malignancies that has relapsed or remains refractory after prior allogeneic hematopoietic cell transplant (HCT):
- •ALL, AML, Myeloid Sarcoma, CML, Juvenile myelomonocytic leukemia (JMML), myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL)
- •Has a suitable single haplotype matched (≥ 3 of 6) family member donor.
- •Does not have any other active malignancy other than the one for which this transplant is indicated.
- •If prior central nervous system (CNS) leukemia, it must be treated and in CNS complete remission (CR)
- •Does not have current uncontrolled bacterial, fungal, or viral infection.
- •Patient must fulfill pre-transplant evaluation:
- •Left ventricular ejection fraction > 40%, or shortening fraction ≥ 25%.
- •Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m
- •Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing.
- •Karnofsky or Lansky (age-dependent) performance score ≥ 50 (See Appendix A).
- •Bilirubin ≤ 3 times the upper limit of normal for age.
- •Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age.
- •Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
- •Not breast feeding
- •DONOR: At least single haplotype matched (≥ 3 of 6) family member
- •DONOR: At least 18 years of age.
- •DONOR: HIV negative.
- •DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
- •DONOR: Not breast feeding.
- •DONOR: Regarding donation eligibility, is identified as either:
- •Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
- •Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.
排除标准
- 未提供
研究组 & 干预措施
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: Cyclophosphamide (Drug)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: Fludarabine (Drug)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: G-CSF (Biological)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: Interleukin-2 (Biological)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: Melphalan (Drug)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: Thiotepa (Drug)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: Rituximab (Drug)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: Natural killer cell therapy (Biological)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: T-cell depleted HPC transplant (Biological)
Participants
Participants undergo a conditioning regimen with cyclophosphamide, fludarabine, aldesleukin (interleukin-2), natural killer cell therapy, anti-thymocyte globulin, rituximab, thiotepa, and melphalan prior to transplantation of T-cell depleted HPC transplant on day 0 and CD45RA-depleted HPC transplant on day 1. Beginning Day 6 post-transplant, patients receive G-CSF daily until ANC recovers to normal level.
干预措施: CD45RA-depleted HPC transplant (Biological)
结局指标
主要结局
Percentage of Participants Engrafted by Day 42 Post-transplant
时间窗: Day 42 post transplantation
To estimate engraftment by day +42 post-transplant in patients who receive CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced intensity conditioning regimen that includes haploidentical NK cells. Engraftment is defined as the first of 3 consecutive tests performed on different days of an ANC ≥ 500/mm\^3 with evidence of donor cell engraftment.
次要结局
- Incidence of Malignant Relapse(one year post transplantation)
- Event-free Survival (EFS)(one year post transplantation)
- Overall Survival (OS)(one year post transplantation)
- Incidence and Severity of Acute GvHD(100 days post transplantation)
- Incidence and Severity of Chronic GvHD(one year post transplantation)
- Rate of Transplant-related Mortality (TRM)(100 days post transplantation)