A Phase II Open-Label Study of UM171-Expanded Cord Blood Transplantation in Patients With High and Very High Risk Acute Leukemia/Myelodysplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 3
- 主要终点
- Adverse events of ECT-001-CB
研究概览
简要总结
Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high transplant related mortality. UM171, a novel and potent agonist of hematopoietic stem cell self renewal could solve this major limitation, allowing for CB's important qualities as lower risk of chronic GVHD and relapse to prevail. In a previous trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe. UM171 expanded CB was associated with a median neutrophil recovery at day (D)+18 post transplant. Amongst 22 patients who received a single UM171 CB transplant with a median follow-up of 18 months, risk of TRM (5%) and grade 3-4 acute GVHD (10%) were low. There was no moderate-severe chronic GVHD. Thus, overall and progression free survival at 12 months were impressive at 90% and 74%, respectively. The UM171 expansion protocol allowed access to smaller, better HLA matched CBs as >80% of patients received a 6-7/8 HLA matched CB. Interestingly there were patients with high-risk hematologic malignancies and multiple comorbidities (5 patients who had already failed an allogeneic transplant and 5 patients with refractory/relapsed acute leukemia/aggressive lymphoma). Despite this high risk population, progression was 20% at 12 months.
This new study seeks to test a similar strategy in a group of patients with high risk acute leukemia/myelodysplasia.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •High and very high-risk hematologic malignancy defined as:
- •Acute Myeloid Leukemia (Primary induction failure, Chemorefractory relapse, Relapse after allogeneic or autologous transplant, High risk AML in CR1, ≥ CR2)
- •Acute Lymphoid leukemia (Primary induction failure, High risk ALL in CR1, ≥ CR2, Chemorefractory relapse, Relapse after allogeneic or autologous transplant)
- •Myelodysplastic syndrome (Relapse after allogeneic or autologous transplant, ≥10% blasts within 30 days of start of conditioning regimen, Poor and very poor cytogenetics abnormalities, CMML with HCT-specific CPSS score high or intermediate-2, Stable disease, Progressive disease while on azacitidine).
- •Chronic myelogenous leukemia (Patients who progressed to blast crisis)
- •Availability of 2 CBs ≥ 4/6 HLA match with pre-freeze CD34+ cell count ≥0.5 x 10E5/kg and TNC≥1.5 x 10E7/kg
- •Karnofsky ≥
- •LVE fraction ≥ 40% or fractional shortening >22%
- •FVC, FEV1 and DLCOc ≥ 50% of predicted
- •Bilirubin < 2 x ULN; AST and ALT ≤ 2.5 x ULN; alkaline phosphatase ≤ 5 x ULN.
- •Creatinine < 2.0 mg/dl.
- •HCT-CI ≤3 if patients have ≥5% blasts in the bone marrow and HCT-CI ≤5 if 60-65 years old.
排除标准
- •Allogeneic myeloablative transplant within 6 months.
- •Autologous hematopoietic stem cell transplant within 6 months.
- •Active or recent invasive fungal infection.
- •Presence of a malignancy other than the one for which the UCB transplant is being performed and the expected survival related to the malignancy is estimated to be less than 75% at 5 years.
- •HIV positivity.
- •Hepatitis B or C infection with measurable viral load.
- •Liver cirrhosis.
- •Pregnancy, breastfeeding or unwillingness to use appropriate contraception.
- •Any abnormal condition or laboratory result that is considered by the principal investigator capable of altering patient condition or study outcome.
- •Active central nervous system involvement.
- •Chloroma > 2 cm.
研究组 & 干预措施
ECT-001-Expanded CB
Patients will receive a myeloablative conditioning regimen.
The cord to be expanded will undergo CD34+ selection. The CD34- product is cryopreserved and will be thawed and infused on Day +1 post-transplant. The CD34+ product will be placed in a closed culture with UM171 for a 7-day expansion and is infused on Day 0.
Patients will receive standard supportive care and GVHD prophylaxis (such as MMF and tacrolimus).
干预措施: ECT-001-CB (UM171-Expanded Cord Blood Transplant) (Biological)
结局指标
主要结局
Adverse events of ECT-001-CB
时间窗: 2 years post-transplant
All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)
Relapse-free survival
时间窗: At 2-year post-transplant
RFS will be measured from time of transplant until disease relapse, death or last follow-up
Adverse events of ECT-001-CB
时间窗: 100 days post-transplant
All AEs will be graded in severity according to the modified (for HSCT) CTCAE (v. 5.0)
Relapse-free survival
时间窗: At 1-year post-transplant
RFS will be measured from time of transplant until disease relapse, death or last follow-up
次要结局
- Time to Neutrophil and Platelet engraftment(First 60 days)
- Incidence of transplant related mortality(At 1-year post-transplant)
- Incidence of GVHD(At 2 years post-transplant)
- Incidence of grade 3 or higher infectious complications(At 2 years post-transplant)
- Incidence of pre-engraftment/engraftment syndrome requiring therapy(At 2 years post-transplant)
- GRFS and CRFS(At 2-year post-transplant)
- Incidence of transplant related mortality(At day 100 post-transplant)
- GRFS and CRFS(At 1-year post-transplant)