Peritransplant Ruxolitinib for Patients With Primary and Secondary Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Incidence of grade II-IV graft versus host disease (GVHD) in myelofibrosis patients
研究概览
简要总结
This phase II trial studies how well administering ruxolitinib before, during, and after allogeneic hematopoietic stem cell transplantation works in preventing graft versus host disease and improving transplant outcomes in patients with primary and secondary myelofibrosis. Donor hematopoietic stem cell transplantation (HSCT) is currently the only treatment with proven curative potential for myelofibrosis, however, myelofibrosis patients have a high risk for developing graft versus host disease post-transplant. Graft versus host disease is a condition where the transplanted cells from a donor can attack the body's normal cells. Ruxolitinib, a janus-associated kinase (JAK) inhibitor, is known to decrease inflammatory signals, which may reduce spleen size and decrease symptoms such as night sweats and weight loss. Administering ruxolitinib before, during, and after transplant may decrease the incidence and severity of graft versus host disease, increase survival, and improve quality of life in patients with primary and secondary myelofibrosis.
详细描述
OUTLINE:
PART 1: Patients receive ruxolitinib orally (PO) starting 8 weeks prior to hematopoietic stem cell transplantation (HSCT) and continuing until approximately 14 days prior to conditioning regimen, then tapered per the treating clinician until day -4 in the absence of disease progression or unacceptable toxicity. Patients who join a different research study for Part 2 have their collected data and samples from Part 1 carried over to the new protocol.
PART 2: Patients are assigned to either a high (myeloablative) or reduced intensity conditioning regimens per the clinical provider together with the Clinical Coordinators Office (CCO):
MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide intravenously (IV) on days -7 and -6 and busulfan IV over 3 hours on days -5 to -2. Patients with umbilical cord blood (UCB) as their transplant source also receive fludarabine IV over 30 minutes on days -8 to -6. Treatment continues in the absence of disease progression or unacceptable toxicity.
REDUCED INTENSITY CONDITIONING: Patients receive fludarabine IV over 30 minutes on days -6 to -2 and melphalan IV over 15-30 minutes on days -3 and -2. Patients with UCB as their transplant source also undergo total body irradiation (TBI) on day -1. Treatment continues in the absence of disease progression or unacceptable toxicity.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years
- •JAK INHIBITOR ADMINISTRATION INCLUSION: (PART I)
- •Disease criteria:
- •Diagnosis of primary myelofibrosis (PMF) as defined by the 2016 World Health Organization classification system or diagnosis of secondary myelofibrosis (MF) as defined by the International Working Group (IWG) for Myeloproliferative Neoplasms Research and Treatment criteria
- •Patients meeting the criteria for intermediate-1, intermediate-2 or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS) or DIPSS plus
- •Ability to understand and the willingness to sign a written informed consent document
- •Patient must be a potential hematopoietic stem cell transplant candidate as assessed by the consenting physician
- •Patient must be willing to start ruxolitinib within a 6-month time period
- •ALLOGENEIC STEM CELL TRANSPLANT INCLUSION: (PART II)
- •Meeting criteria for part 1, as above, at time of initiation of ruxolitinib, including the ability to understand and willingness to sign a written informed consent. Patients arriving to our institution for transplant and not enrolled in part 1 may still be enrolled in part 2 if part 1 criteria are met. These patients will have part 1 endpoints transcribed from medical records
- •Received ruxolitinib for at least 8 weeks immediately prior to conditioning and be willing to continue until 9-12 months post-transplant as tolerated
- •Performance status score: Karnofsky >= 70
- •Calculated creatinine clearance using the Cockcroft-Gault formula or 24 hour (hr) urine creatinine clearance must be > 60 ml/min
- •Total serum bilirubin must be < 3 mg/dL unless the elevation is thought to be due to Gilbert's disease or hemolysis
- •Transaminases must be < 3 x the upper limit of normal
- •Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, and the degree of portal hypertension. Patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded
- •Diffusion capacity of lung for carbon monoxide (DLCO) corrected > 60% normal. May be not be on supplemental oxygen
- •Left ventricular ejection fraction > 40% OR shortening fraction > 26%
- •Comorbidity index < 5 at the time of pre-transplant evaluation
排除标准
- •JAK INHIBITOR ADMINISTRATION EXCLUSION: (PART I)
- •Contraindication to receiving ruxolitinib including:
- •Patients who have known hypersensitivity to JAK inhibitors
- •Clinical or laboratory evidence of significant renal or hepatic impairment including cirrhosis
- •Active uncontrolled infection
- •Known human immunodeficiency virus (HIV) positivity
- •Women who are pregnant or trying to conceive
- •Caution should be used in patients with platelets < 100 though adjustments in dose can be made to accommodate anyone with platelets > 50
- •History of prior allogeneic transplant
- •Leukemic transformation (> 20% blasts)
- •ALLOGENEIC STEM CELL TRANSPLANT EXCLUSION: (PART II)
- •Uncontrolled viral or bacterial infection at the time of transplant data review and consent conference
- •Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
- •History of HIV infection
- •Pregnant or breastfeeding
- •Patients without a human leukocyte antigen (HLA)-identical sibling donor, 10 of 10 HLA-matched or 9 of 10 allele mismatched unrelated donor, or umbilical cord blood units that meet transplant criteria
研究组 & 干预措施
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Total-Body Irradiation (Radiation)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Computed Tomography (Procedure)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Echocardiography (Procedure)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Bone Marrow Aspiration and Biopsy (Procedure)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Ultrasound Imaging (Procedure)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Cyclophosphamide (Drug)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Mycophenolate Mofetil (Drug)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Tacrolimus (Drug)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Busulfan (Drug)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Methotrexate (Drug)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Fludarabine (Drug)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Melphalan (Drug)
Treatment (ruxolitinib, conditioning, HSCT, GVHD prophylaxis)
See detailed description.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Incidence of grade II-IV graft versus host disease (GVHD) in myelofibrosis patients
时间窗: Up to day 100
The probability of grade II-IV acute GVHD observed in this study will be compared to a fixed benchmark, this fixed benchmark derived from the results of a previous study (FH Protocol 9033).
次要结局
- Incidence of grade III-IV GVHD(Up to day 100)
- Time to neutrophil (ANC > 500) engraftment(Day 100)
- Incidence of relapse(At 1 year)
- Time to platelet (> 20,000) engraftment(Day 100)
- Incidence of chronic GVHD(At 1 and 2 years)
- Overall survival rate (OS)(At 1 and 2 years)
- Incidence of primary and secondary graft failure(6 months)
- Non-relapse mortality (NRM)(Day 100 and 1 year)