Haploidentical Allogeneic Peripheral Blood Transplantation: Clinical Trial and Laboratory Correlates Examining Checkpoint Immune Regulators' Expression
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experienced Donor-Recipient Chimerism Following Transplant at Days 30, 60, and 90.
研究概览
简要总结
The standard Johns Hopkins' regimen will be used in study subjects, with the use of donor peripheral blood stem cells, rather than marrow. Clinical outcomes will be defined while focusing efforts on immune reconstitution focusing on immune checkpoint regulators after a related haploidentical stem cell transplant.
详细描述
We propose a clinical trial to define clinical endpoints, including engraftment, 100-day survival and one year survival (Objective #1). We will characterize the incidence, prevalence and function of immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). We will correlate these laboratory results with clinical outcomes and the incidence of GVHD. As an exploratory aim, in those patients experiencing GVHD and requiring treatment, we will define the frequency/expression of checkpoint regulator expression and correlate these results with the patient's response to GVHD 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age: less than 75 years
- •The patient must be approved for transplant by the treating transplant physician. This includes completion of their pre-transplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedure (SOP) (DHMC SOP - Pre-transplant Evaluation of allogeneic recipient (Appendix).
- •The patient must have a disease (listed below) with treatment-responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:
- •Acute leukemia - Acute Myeloid Leukemia, Acute Lymphocytic Leukemia
- •Chronic leukemia - Chronic Myeloid Leukemia, Chronic Lymphocytic Leukemia
- •Myelodysplasia
- •Myeloproliferative disorder
- •Myelofibrosis
- •Lymphoma - Non-Hodgkin's Lymphoma or Hodgkin's disease
- •Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia
- •Donor availability- the patient must have an identified RELATED haplo-identical donor
- •No Human Immunodeficiency Virus infection or active hepatitis B or C
- •Eastern Cooperative Oncology Group performance status: 0-2
- •Diffusing capacity of carbon monoxide (DLCO) greater than or equal to 40 % predicted
- •Left ventricular ejection fraction greater than or equal to 40%
- •Serum bilirubin < 2x upper limit of normal; transaminases < 3x normal at the time of transplant
- •No active or uncontrollable infection
- •In female, a negative pregnancy test if experiencing menstrual periods
- •No major organ dysfunction precluding transplantation
- •No evidence of an active malignancy that would limit the patient's survival to less than 2 years. (If there is any question, the PI can make a decision).
排除标准
- •Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
- •Major anticipated illness or organ failure incompatible with survival from bone marrow transplant.
- •History of refractory systemic infection
- •DONOR ELIGIBILITY
- •Human leukocyte antigen (HLA) haplo-identical matched related.
- •The donor must be healthy and must be willing to serve as a donor, based on standard National Marrow Donor Program (NMDP) guidelines and DHMC SOP - Donor Evaluation (Appendix)
- •The donor must have no significant co-morbidities that would put the donor at marked increased risk
- •There is no age restriction for the donor
- •Informed consent must be signed by donor
- •DONOR EXCLUSION CRITERIA
- •The NMDP guidelines for exclusion criteria will be used (Appendix). In addition, the following donors are NOT eligible:
- •Pregnant or lactating donor
- •HIV or active Hep B or C in the donor
- •Donor unfit to receive G-CSF and undergo apheresis
- •A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible
研究组 & 干预措施
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
干预措施: Cyclophosphamide (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
干预措施: Total Body Irradiation (Radiation)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
干预措施: Fludarabine (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
干预措施: Tacrolimus (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
干预措施: Peripheral Blood Transplant (Procedure)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
干预措施: g-csf (Drug)
Johns Hopkins' conditioning regimen
Cyclophosphamide, fludarabine, total body irradiation, immune suppression including tacrolimus and cellcept, Granulocyte colony-stimulating factor (G-CSF), and peripheral blood transplant
干预措施: cellcept (Drug)
结局指标
主要结局
Number of Participants Who Experienced Donor-Recipient Chimerism Following Transplant at Days 30, 60, and 90.
时间窗: Days 30, 60, and 90 post-peripheral blood transplant
Define subjects who experience donor-recipient chimerism following transplant at days 30, 60 and 90. All patients were assessed for donor-recipient chimerism at days 30, 60, and 90, but only one patient experienced chimerism. Day 90 for this patient is reported.
Number of Participants Who Survived to 100-Days Post-transplant
时间窗: 100 days post date of peripheral blood transplant
Define 100-day survival of subjects
Number of Participants Who Survived to One Year Post-Transplant.
时间窗: One year post date of peripheral blood transplant
Define one year survival of subjects
Number of Participants Who Experienced a Successful Engraftment
时间窗: Post-peripheral blood transplant
Define number of subjects who experience a successful engraftment: Defined as absolute neutrophil count \> 500/mm3 and platelets \> 20,000/mcl for three consecutive days (count first day as engraftment)
Number of Participants Who Achieved a Response to Treatment at 100 Days
时间窗: 100 days post-peripheral blood transplant
Define response to treatment at 100 days post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
Number of Participants Who Achieved a Response to Treatment at One Year
时间窗: One year post-peripheral blood transplant
Define response to treatment at one year post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
Number of Participants Who Experienced Toxicities Associated With This Treatment Regimen
时间窗: Post-peripheral blood transplant
Define subjects who experienced toxicities associated with this treatment regimen
Number of Participants Who Had Incidence of Acute GVHD
时间窗: Post-peripheral blood transplant
Define subjects who had incidence of acute GVHD
Number of Participants Who Had Incidence of Chronic GVHD
时间窗: Post-peripheral blood transplant
Define subjects who had incidence of chronic GVHD
Number of Participants Who Experienced Treatment-Related Mortality Within the First 100 Days
时间窗: 100 days post-peripheral blood transplant
Define subjects who experienced treatment-related mortality within the first 100 days post-peripheral blood transplant
次要结局
- Myeloid-derived Suppressor Cells (MDSCs) After Graft vs. Host Disease (GVHD) Diagnosis - Checkpoint Regulator Expression(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- MDSCs After GVHD Diagnosis - Frequency(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- Immune Checkpoint Regulators - Incidence(Days 30, 60, and 90 post-transplant)
- MDSCs After GVHD Diagnosis - Peripheral Blood Mononuclear Cells(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- MDSCs After GVHD Diagnosis - Myeloid Subsets Using Flow Cytometry(Post-transplant through study completion or death, assessed up to 3 years post-transplant)
- Immune Checkpoint Regulators - Function(Days 30, 60, and 90 post-transplant)
- Immune Checkpoint Regulators - Prevalence(Days 30, 60, and 90 post-transplant)
研究者
Kenneth Meehan
Principal Investogator- Kenneth Meehan, MD Staff Physician
Dartmouth-Hitchcock Medical Center