Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Event Free Survival (EFS) for Research Participants
研究概览
简要总结
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA)-matched related/sibling donor (MSD), matched unrelated donor (MURD) or killer-immunoglobulin receptors (KIR) ligand mismatched haploidentical donor identified, will receive an umbilical cord blood transplantation (UCBT) using a myeloablative preparative regimen.
The preparative regimen includes fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (10.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2. Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.
详细描述
The primary objectives is to estimate the event-free survival (EFS) at one-year post-transplant for research participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT) using single unit umbilical cord blood (UCB).
Secondary objectives are:
- Describe the clinical outcome of patients undergoing a double unit UCBT.
- Estimate the incidence and severity of acute and chronic graft versus host disease (GVHD) of patients enrolled in the research arm.
- Estimate the incidence and time to neutrophil and platelet engraftment among patients enrolled in the research arm.
- Estimate the incidence of transplant related mortality (TRM) and transplant related morbidity in the first 100 days after transplantation among patients enrolled in the research
Exploratory Objectives are:
- Assess the relationship between pre-transplant minimal residual disease (MRD) with transplant outcomes.
- Record immune reconstitution parameters, including chimerism analysis, quantitative lymphocyte subsets, T cell receptor excision circle (TREC) and spectratyping. Immunophenotyping and functional assays of T, B and NK cells and lymphocytes will also be evaluated.
- Evaluate the determinants of engraftment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 old.
- •Has a partially HLA-matched single or double UCB product
- •High-risk hematologic malignancy.
- •High risk ALL in CR1, ALL in High risk CR2, ALL in CR3 or subsequent.
- •AML in high risk CR1, AML in CR2 or subsequent
- •AML in first relapse with < 25% blasts in BM
- •Therapy related AML, with prior malignancy in CR > 12mo
- •MDS, primary or secondary
- •NK cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
- •CML in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor.
- •Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT.
- •Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize stem cells for autologous HCT.
- •All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
- •Patient must fulfill pre-transplant evaluation:
- •Cardiac shortening fraction ≥ 26%.
- •Creatinine clearance ≥ 70 ml/min/1.73m
- •Forced vital capacity (FVC) ≥ 50% of predicted value or pulse oximetry ≥ 92% on room air.
- •Karnofsky (≥ 16 years) or Lansky (<16 years) performance score ≥ 70
- •Bilirubin ≤ 2.5 mg/dL.
- •Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age.
- •Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age.
排除标准
- •Patient has a suitable MSD, volunteer MURD, or KIR mismatched haploidentical donor available in the necessary time for stem cell donation.
- •Patient has any other active malignancy other than the one for which HCT is indicated.
- •Patient had a prior allogeneic HCT
- •Patient had an autologous HCT within the previous 12 months.
- •Patient is pregnant as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment.
- •Patient is lactating
- •Patient has Down Syndrome
- •Patient has a current uncontrolled bacterial, fungal, or viral infection per the judgment of the PI.
研究组 & 干预措施
Research Arm
Participant with high-risk hematologic malignancies undergoing Hematopoietic Cell Transplantation, who do not have a suitable Human Leukocyte Antigen -matched related/sibling donor, Matched Unrelated Donor or Killer immunoglobulin receptors ligand mismatched haploidentical donor identified, will receive a single UCB unit.
Intervention: Preparative Regimen
干预措施: Preparative Regimen (Drug)
Observation Arm
Patients requiring two UCB units will be eligible for UCBT01 on the observational arm.
Intervention: Preparative Regimen
干预措施: Preparative Regimen (Drug)
结局指标
主要结局
Event Free Survival (EFS) for Research Participants
时间窗: 1 year post-transplant
Estimate EFS for research participants at one-year post transplant by using single unit umbilical cord blood. The event is defined as relapse, graft failure, death due to any cause. The number of participants who did not experience any of those events (relapse, graft failure, death due to any cause) at year 1 post-transplant was given.
次要结局
- Number of Observational Arm Participants Engrafted(1 year)
- Number of Observational Arm Patients Who Relapsed(1 year)
- Number of Deaths of Observational Arm Patients(1 year)
- Number of Observational Arm Patients With Transplant-related Mortality (TRM)(First 100 days)
- Number of Participants With Acute GVHD(1 year)
- Number of Participants With Chronic GVHD(1 year)
- Time to Engraftment of Research Arm Participants(first 100 days post transplant)
- Incidence of Transplant-related Mortality (TRM)(first 100 days post transplant)
- The Number of Participants With Transplant-related Morbidity(first 100 days post transplant)