Dose Escalation Study With Extension of Inducible Regulatory T Cells (iTregs) in Adult Patients Undergoing Non-Myeloablative HLA Identical Sibling Donor Peripheral Blood Stem Cell Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 2
- 主要终点
- Incidence of grade 3-5 infusional toxicity
研究概览
简要总结
This is a phase I single center dose escalation study with an extension at the best available dose to determine the tolerability of inducible regulatory T cells (iTregs) when given to adult patients undergoing non-myeloablative HLA-identical sibling donor peripheral blood stem cell (PBSC) transplantation for the treatment of a high risk malignancy. Up to 5 dose cohorts will be tested. Once the tolerable dose is determined for iTregs, enrollment will continue with an additional 10 patients using sirolimus/Mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis to gain further safety information and to provide pilot data in this treatment setting.
详细描述
Co-enrollment in University Of Minnesota protocol MT2001-10 is required and transplantation will be according to that protocol with iTregs administered the morning of day 0 followed no sooner than 4 hours later by the PBSC transplantation.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 - 75 years of age with an HLA-identical sibling donor
- •One of the following disease categories:
- •Acute myelogenous leukemia - high risk CR1 (as evidenced by preceding MDS, intermediate to high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- •Acute lymphocytic leukemia - high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] or >1cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- •Chronic myelogenous leukemia all types except blast crisis (note treated blast crisis in chronic phase is eligible)
- •Non-Hodgkin lymphoma or Hodgkin lymphoma demonstrating chemosensitive disease
- •Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion dependency or increased risk for infections
- •Performance status: Karnofsky ≥ 60%
- •Adequate organ function within 28 days of study enrollment defined as:
- •Liver: SGOT and SGPT < 5.0 x ULN; total bilirubin < 3 x ULN
- •Renal: serum creatinine < 2.0 mg/dl or glomerular filtration rate (GFR) > 40 mL/min/1.73m
- •Patients with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2
- •Albumin: > 2.5 g/dL
- •Cardiac: No decompensated CHF or uncontrolled arrhythmia; ejection fraction > 35% within 6 weeks prior to study enrollment
- •Pulmonary: No O2 requirements; DLCO > 30% predicted within 6 weeks prior to study enrollment
- •If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy and responsive disease and be cleared by Infectious Disease
- •Sexually active females of child bearing potential and males must agree to use effective contraception for the duration of the transplant period
- •Voluntary written consent
排除标准
- •Pregnancy or breast feeding - women of childbearing potential must have a negative pregnancy test within 28 days of study enrollment.
- •Prior myeloablative transplant within previous 3 months of study enrollment.
- •Evidence of HIV infection or known HIV positive serology.
- •Active serious infection.
研究组 & 干预措施
Cohort 1
Administered 3 x 10^6 iTregs/kg infusion
干预措施: iTreg (Biological)
Cohort 2
Administered 3 x 10^7 iTregs/kg infusion
干预措施: iTreg (Biological)
Cohort 3
Administered 3 x 10^8 iTregs/kg infusion
干预措施: iTreg (Biological)
Cohort 4
Administered 10 x 10^8 iTregs/kg infusion
干预措施: iTreg (Biological)
Cohort 5 Extension
Administered 10 x 10^8 iTregs/kg or best available dose using sirolimus/MMF as graft-versus-host disease (GVHD) prophylaxis. Immunosuppression will consist of a combination of sirolimus and mycophenolate mofetil (MMF). Sirolimus will be administered starting at day -3 with 8mg-12mg oral loading dose followed by single dose 4 mg/day. MMF will be administered starting on day -3 at a dose of 3 gram/day divided in 2 or 3 doses. Intravenous (IV) route between days -3 and +5, then may change to PO between days +6 and +30. Stop MMF at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD.
干预措施: iTreg (Biological)
结局指标
主要结局
Incidence of grade 3-5 infusional toxicity
时间窗: Within 48 Hours After iTregs Administration
Targeted adverse events and unexpected events not explained by the PBSCT or disease will be collected \[(1-4 hours after the iTreg infusion and before the PBSCT at day 0) and 24 hours and 48 hours after the iTreg infusion (+/- 2 hours)\]
次要结局
- Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD)(Day 100)
- Incidence of chronic graft-versus-host disease (GVHD)(12 Months)
- Relapse of Disease(12 Months)
- Survival(Day 100)