Pilot Study of JAK Inhibitor Therapy Followed by Reduced Intensity Haploidentical Transplantation for Patients With Myelofibrosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Probability of primary and secondary graft failure
研究概览
简要总结
This initial cohort of this phase II trial studied the outcomes of using a JAK inhibitor prior to reduced intensity haploidentical (Haplo) transplantation for the treatment of primary or secondary myelofibrosis (MF). The primary risk of using Haplo HCT in patients with MF is graft failure. In the first cohort, all patients engrafted. There were no instances of graft failure. However, a large number of patients did have graft versus host disease as a complication of their transplant. JAK inhibitors have since been approved for the indication of graft versus host disease treatment. And we are also using them for graft versus host disease prevention in a study of MF patients with sibling and unrelated donors. Therefore, we are opening a new cohort of the current study using the JAK inhibitor prior to, during and after Haplo transplant. Our goal is to decrease graft versus host disease in patients receiving a Haplo MF transplant without increasing the risk of graft failure.
详细描述
OUTLINE: Cohort 1 is now closed and all patients will be enrolled on Cohort 2.
COHORT I:
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of hematopoietic cell transplantation (HCT) conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan intravenously (IV) over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo total-body irradiation (TBI) on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PART 1: JAK INHIBITOR ADMINISTRATION INCLUSION CRITERIA
- •Age between 18 and 70 years
- •Diagnosis of primary myelofibrosis (PMF) as defined by the 2016 World Health Organization classification system or diagnosis of secondary 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 the Dynamic International Prognostic Scoring System (DIPSS)-plus scoring system (DIPSS may be used if all data from DIPSS are not available)
- •Ability to understand and the willingness to sign a written informed consent document (or legally authorized representative)
- •Patient must be a potential hematopoietic stem cell transplant candidate
- •PART 2: ALLOGENEIC STEM CELL TRANSPLANT INCLUSION CRITERIA
- •Meeting criteria for 1st phase as above, at time of initiation of JAK inhibitor, including ability to understand and willingness to sign a written informed consent (or legally authorized representative). Patients arriving to our institution for transplant and not enrolled in Part 1 may still be enrolled in Part 2 if Part 1 criteria met. These patients will have Part 1 endpoints transcribed from medical records
- •Received JAK inhibitor for at least 8 weeks immediately prior to conditioning and be willing to continue until 9-12 months post-transplant as tolerated
- •Karnofsky performance status score >= 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 > 3 mg/dL, and symptomatic biliary disease will be excluded
- •Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 60% normal; may not be on supplemental oxygen
- •Left ventricular ejection fraction > 40% OR shortening fraction > 26%
- •Comorbidity Index < 5 at the time of pre-transplant evaluation
- •DONOR: Patients must be screened prior to transplant for donor-specific anti-HLA antibodies (DSA). Patients with DSA will be reviewed by the principal investigator and considered for desensitization treatment
- •DONOR: Children are preferred over siblings and parents
- •DONOR: Younger donors are preferred over older donors
- •DONOR: ABO matched donors are preferred over minor ABO mismatched and over major ABO mismatch donors
排除标准
- •PART 1: JAK INHIBITOR ADMINISTRATION EXCLUSION CRITERIA
- •Contraindication to receiving a JAK inhibitor 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)
- •PART 2: ALLOGENEIC STEM CELL TRANSPLANT EXCLUSION CRITERIA
- •Uncontrolled viral or bacterial infection at the time of study enrollment
- •Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
- •Known HIV positivity
- •Pregnant or breastfeeding
- •Availability of an human leukocyte antigen (HLA)-identical or 1-allele-mismatched related donor or an HLA 10 of 10 matched unrelated donor
研究组 & 干预措施
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: JAK Inhibitor (Drug)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Recombinant Granulocyte Colony-Stimulating Factor (Biological)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Total-Body Irradiation (Radiation)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Computed Tomography (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Bone Marrow Biopsy (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Bone Marrow Aspiration (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Biospecimen Collection (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Echocardiography Test (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Multigated Acquisition Scan (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: JAK Inhibitor (Drug)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Recombinant Granulocyte Colony-Stimulating Factor (Biological)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Total-Body Irradiation (Radiation)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Computed Tomography (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Magnetic Resonance Imaging (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Bone Marrow Biopsy (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Bone Marrow Aspiration (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Biospecimen Collection (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Echocardiography Test (Procedure)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Multigated Acquisition Scan (Procedure)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Cyclophosphamide (Drug)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Fludarabine (Drug)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Melphalan (Drug)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Mycophenolate Mofetil (Drug)
Cohort I (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Tacrolimus (Drug)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Cyclophosphamide (Drug)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Fludarabine (Drug)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Melphalan (Drug)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Mycophenolate Mofetil (Drug)
Cohort II (JAK inhibitor, conditioning, GVHD prophylaxis)
JAK INHIBITOR THERAPY: Patients receive a JAK inhibitor at least 8 weeks prior to the start of HCT conditioning through day -4 before transplantation. Additionally, patients receive a JAK inhibitor following transplantation beginning day 5 through 9-12 months after transplant.
CONDITIONING: Patients receive melphalan IV over 1 hour on day -5, fludarabine IV over 30-60 minutes on days -5 to -2, and undergo TBI on day -1 or day -1 and day 0.
TRANSPLANT: Patients receive peripheral blood stem cell infusion on day 0.
GVHD PROPHYLAXIS: Patients then receive cyclophosphamide IV over 3 hours on days 3-4, tacrolimus IV beginning day 5 then PO for about 6 months, mycophenolate mofetil PO BID or TID beginning day 5 for 6 weeks, and G-CSF SC beginning day 7 until neutrophil recovery is > 1,500/mm^3.
All patients undergo MRI, CT, bone marrow biopsy and aspiration and blood sample collection throughout the trial. Patients also undergo ECHO or MUGA on the trial.
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Probability of primary and secondary graft failure
时间窗: Up to 5 years
Primary graft failure is defined as failure to achieve an absolute neutrophil count of \> 500/ul by 42 days after bone marrow or peripheral blood stem cell transplantation. Secondary graft failure is defined as cytopenias after initial engraftment, with (a) donor chimerism of \< 5% or (b) falling donor chimerism with intervention such as second transplant or donor lymphocyte infusion or (c) patient death due to cytopenias, and fall in donor chimerism, even if chimerism is \> 5%. Exclusion criteria for diagnosis of graft failure are (a) disease relapse, (b) graft-versus-host disease, and (c) other causes of cytopenias such as, viral infection and drug toxicity.
次要结局
- Incidence of relapse(At 1 year)
- Incidence of severe (grade 3 or 4) cytokine release syndrome(Up to 5 years)
- Non-relapse mortality (NRM)(Day 100)
- Overall survival(3 years)
- Incidence of grade II-IV acute graft versus host disease (GVHD)(Up to 5 years)
- NRM(1 year)
- Incidence of grade III-IV acute GVHD(Up to 5 years)
- Incidence of moderate-severe chronic GVHD(Up to 5 years)
- Overall survival(1 year)