PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- Determine the Optimal Dose of VIC-1911 When Given in Combination With Standard Immunosuppressive Therapy in Adult Patients Undergoing Myeloablative Stem Cell Transplantation.
研究概览
简要总结
This is a single-arm, phase I/II, study of PTCy/sirolimus plus VIC-1911 to prevent GVHD and relapse after Allogeneic Hematopoietic Cell Transplantation (alloHCT).
详细描述
Determination of the optimal dose during the Phase I trial is based on Dose Limiting Toxicity for safety and reduction of CD4+, pH3ser10+ T cells (phosphorylated histone 3 serine 10 is a biomarker of Aurora kinase A activity) for efficacy. Phase II will be powered to improve grade III-IV acute graft-versus-host disease and relapse after alloHCT, compared to historical estimates at the University of Minnesota.
Patients will receive myeloablative conditioning (MAC) with total body irradiation (TBI) followed by infusion of HLA-matched related or unrelated peripheral blood stem cells (PBSC) on day 0. Cyclophosphamide will be administered on days +3 and +4. Sirolimus targeting 8-12ng/ml will begin on day +5 until day +365. VIC-1911 will be administered as 25 mg, 50 mg, or 75 mg orally BID from day +5 to day +45 according to the rules of our phase I study. The lowest biologically active and safe dose of VIC-1911 will be identified as the recommended phase II dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of
- •acute leukemia in complete remission, or
- •myelodysplasia with <5% blasts, or
- •myeloproliferative neoplasm/myelofibrosis with <5% marrow or circulating blasts
- •chemosensitive Hodgkin or non-Hodgkin lymphoma
- •Age 18 years or older
- •Performance status of ≥ 80% Karnofsky
- •Adequate organ function within 28 days of study registration defined as:
- •left ventricular ejection fraction ≥ 45%
- •pulmonary function with FEV1, FVC, and DLCO ≥ 50% predicted
- •AST and ALT < 2 times upper limit of normal
- •Total bilirubin <1.5 times the upper limit of normal. If the patient is suspected of having Gilbert syndrome, they require prior approval of the medical monitor
- •creatinine clearance ≥ 50cc/min
- •no active/uncontrolled infection
- •negative HIV, HBV and HCV
- •ferritin < 2000 ng/ml
- •Patients able to tolerate oral medication
- •Women of childbearing potential and men with partners of child-bearing potential must agree to use of contraception for the duration of treatment through 60 days after the last treatment of VIC-1911 or sirolimus
- •Able to provide written voluntary consent prior to the performance of any research related tests or procedures
排除标准
- •HCT-CI > 4 or unable to receive myeloablative TBI
- •Use of planned post-transplant maintenance therapy to begin prior to day +
- •Patients may receive standard of care maintenance therapies starting at day
- •+75 or later
- •Patients with a history of hypersensitivity to any of the investigational products
- •Pregnant or breastfeeding as agents used in this study are Pregnancy Category
- •o C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations, and Pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Females of childbearing potential must have a negative pregnancy test (serum or urine) within 28 days of study registration.
- •Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 60 days after the last treatment of VIC-1911 or sirolimus
研究组 & 干预措施
PTCy/sirolimus plus VIC-1911
Patients enrolled and treated with PTCy/sirolimus plus VIC-1911
干预措施: VIC- 1911 (Drug)
结局指标
主要结局
Determine the Optimal Dose of VIC-1911 When Given in Combination With Standard Immunosuppressive Therapy in Adult Patients Undergoing Myeloablative Stem Cell Transplantation.
时间窗: 21 days post treatment
The optimal dose will be identified using the EffTox design. The proportion of patients with an average CD4+, pH3ser10+ T cell of \<54%. The minimum desired biologic efficacy is 65% of patients by day 21 (+/- 3 days) with \<30% of patients experiencing a DLT. Data only to reported from arm with maximum tolerated dose.
Progression-free Survival
时间窗: 1 Year
Participant progression-free survival assessed using aGVHD data.
Relapsed Assessment (Phase I)
时间窗: 12 months
Assessment to determine if patient has relapse in MTD arm. Data only to reported from arm with maximum tolerated dose.
次要结局
- Overall Survival (OS)(1 year)
- To Determine the Cumulative Incidences of Acute GVHD(Day 100)
- To Determine the Cumulative Incidences of Chronic GVHD(12 months)
- Progression-free Survival Comparing Graft-Versus-Host Disease-Free (GRFS) to the Standard PTCY Plus Tacrolimus/Mycophenolate Mofetil Regimen From MT2015-29(12 months)
- Progression Free Survival(1 Year)
- Frequency of CMV Reactivation and Disease(Day 100)