Ruxolitinib in Combination With High Dose Therapy and Autologous Stem Cell Transplantation for Myelofibrosis
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 主要终点
- Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death
研究概览
简要总结
To determine the safety of the approach of giving RUXOLITINIB before and after an autologous stem cell transplant, as measured by graft failure or death.
详细描述
This is a pilot, single arm, single center study with no stratification to assess the safety (measured by graft failure or death) and feasibility (measured by adequacy of stem cell collection) of combining ruxolitinib with autologous Hematopoeitic Stem Cell Transplantation (HSCT) in patients with advanced myelofibrosis (MF). Patients will receive a short course of ruxolitinib prior to and during mobilization of HSCT with Filgrastim. Conditioning for the autologous HSCT will consist of Bulsulfan. Post-transplant patients will receive ruxolitinib maintenance.
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
- 否
入选标准
- •Histologically documented diagnosis of MF (idiopathic or post PV/ET)
- •Age 18-75 years
- •Intermediate-2/ high-risk disease as per Dynamic IPSS (DIPSS) criteria or Intermediate-1 risk disease with one of the following features within one year from screening:
- •Red cell transfusion dependency
- •unfavorable Karyotype
- •platelet count <100 x 109/L
- •symptomatic splenomegaly
- •PB blasts > 1%
- •Blasts in PB <20% prior to study enrollment
- •No available suitable matched related (6/6 or 5/6) or unrelated donor (8/8 or 7/8 allele matched) or unwilling or unable to pursue allogeneic stem cell transplant
- •WBC <50,000/ml at screening
- •Able to give informed written consent
- •ECOG Performance status of 0-2
- •Life expectancy >6 months
- •Off all myelofibrosis-related investigational or standard agents (except for ruxolitinib) for at least 4 weeks prior to study enrollment and recovered from all toxicities. If patient is already on ruxolitinib for a minimum of 16 weeks prior to study enrollment, patient can proceed to mobilization and collection
- •Adequate organ function defined as the following (*unless clearly disease related):
- •Adequate renal function - creatinine <2 x ULN
- •Adequate hepatic function - AST/ALT <3 x ULN, Total Bilirubin <3 x ULN, exception is elevated indirect bilirubin attributed to Gilbert's syndrome or hemolysis
- •Adequate hematopoietic function - Platelet ≥50 x 109/L (without transfusion) and ANC ≥1.0 x 109/L
- •LVEF >40% (MUGA or echocardiogram)
- •Adequate pulmonary function with DLCO >40%
排除标准
- •Hypersensitivity to JAK inhibitor
- •Clinical evidence of cirrhosis
- •Leukemic transformation (>20% blasts in PB or BM any time prior to HCT)
- •Platelet count <50 x 109/L
- •Active uncontrolled infection
- •History of another malignancy within 5-years of date of HCT except history of basal cell or squamous cell carcinoma of skin or PV or ET
- •Known HIV positive
- •Woman of childbearing potential unwilling or unable to use adequate contraception Pregnant or nursing females Known active infection with hepatitis A, B or C virus
研究组 & 干预措施
Ruxolitinib / INC 424
Ruxolitinib, Jakafi ®, will be given orally at standard dose daily for 16 weeks pre ASCT and up to 3 months post-ASCT for 10 patients (allowing for 2 additional screen failures). Patients will restart ruxolitinib at 100 days after the ASCT as long as their platelet count is at least 50 x103. For patients whose platelet count is below 50 x103 at day 100, ruxolitinib should be restarted once platelet count reaches 50 x103. The dose of ruxolitinib can be titrated up as per clinical guidelines. PBSC mobilization will include G-CSF 10 mcg/kg/day. HDC for ASCT will consist of IV busulfan 2.0 mg/KBW once daily x 4 for days -5 to -2.
干预措施: RUXOLITINIB / INC 424 (Drug)
Ruxolitinib / INC 424
Ruxolitinib, Jakafi ®, will be given orally at standard dose daily for 16 weeks pre ASCT and up to 3 months post-ASCT for 10 patients (allowing for 2 additional screen failures). Patients will restart ruxolitinib at 100 days after the ASCT as long as their platelet count is at least 50 x103. For patients whose platelet count is below 50 x103 at day 100, ruxolitinib should be restarted once platelet count reaches 50 x103. The dose of ruxolitinib can be titrated up as per clinical guidelines. PBSC mobilization will include G-CSF 10 mcg/kg/day. HDC for ASCT will consist of IV busulfan 2.0 mg/KBW once daily x 4 for days -5 to -2.
干预措施: Filgrastim (Drug)
Ruxolitinib / INC 424
Ruxolitinib, Jakafi ®, will be given orally at standard dose daily for 16 weeks pre ASCT and up to 3 months post-ASCT for 10 patients (allowing for 2 additional screen failures). Patients will restart ruxolitinib at 100 days after the ASCT as long as their platelet count is at least 50 x103. For patients whose platelet count is below 50 x103 at day 100, ruxolitinib should be restarted once platelet count reaches 50 x103. The dose of ruxolitinib can be titrated up as per clinical guidelines. PBSC mobilization will include G-CSF 10 mcg/kg/day. HDC for ASCT will consist of IV busulfan 2.0 mg/KBW once daily x 4 for days -5 to -2.
干预措施: Busulfan (Drug)
结局指标
主要结局
Safety of combining ruxolitinib with autologous HSCT measured by graft failure or death
时间窗: 2 years
Safety of this approach as measured by graft failure or death
次要结局
- CD34 cells(4 years)
- Changes in marrow fibrosis score(at 180 and 365 days post-transplant)
- Time of engraftment for neutrophils and platelets(4 years)
- Rate of engraftment/graft failure(4 years)
- The incidence of serious infectious complications(up to 1 year post transplant)
- Change in FISH allele(at 365 days post-transplant)
- Change in JAK allele(at 365 days post-transplant)
- Rate of response(at 1 year post-transplant)
- The regimen related mortality (RRM)(day 365)
研究者
Marina Kremyanskaya
Assistant Professor
Icahn School of Medicine at Mount Sinai