NCT03421756终止早期 1 期
A Pilot Study Evaluating the Efficacy of Non-Myeloablative Matched Related Donor Peripheral Blood Stem Cell Transplant in Patients With Severe Sickle Cell Disease
Kathleen Dorritie1 个研究点 分布在 1 个国家目标入组 1 人开始时间: 2018年3月29日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Treatment Success
研究概览
简要总结
This is a prospective pilot study of matched-related donor allogeneic stem cell transplantation in adults with severe sickle cell disease using a matched-sibling PBSC graft with a non-myeloablative conditioning regimen (Alemtuzumab).
详细描述
Stem cell transplantation recipients will be given Alemtuzumab, which is a non-myeloablative pre-transplant conditioning regimen. This non-myeloablative therapy uses doses of chemotherapy and radiation to weaken (but not destroy) the patients bone marrow and immune system, while still allowing their body to accept the donor's stem cells. Alemtuzumab will be given 7 days prior to stem cell infusion at 0.03 mg/kg IV, 6 days prior to stem cell infusion at 0.1 mg/kg IV, and 5 thru 3 days prior to stem cell infusion at 0.3 mg/kg IV.
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
- •Patient selection
- •Age > 18 years
- •Patients with Hb SS, Hb SC, Hb Sβ0 genotype
- •Presence of at least 1 of the following manifestations:
- •History of clinically significant neurologic event defined as stroke or any neurological deficit lasting > 24 hours.
- •History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures
- •Three or more pain crises per year in the 2-year period preceding referral (required intravenous pain management in the outpatient or inpatient hospital setting).
- •This may include painful episodes related to priapism, osteonecrosis or any sickle-related complication.
- •An echocardiographic finding of the tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
- •History of osteonecrosis or avascular necrosis of ≥ 2 joints
- •Administration of regular RBC transfusion therapy, defined as receiving 8 or more transfusions per year for > 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
- •History of RBC allo-immunization but without detectable allo-antibodies.
- •Evidence of sickle hepatopathy or iron overload in patients who received ≥ 8 packed RBC transfusions for ≥ 1 year or have received ≥ 20 cumulative packed RBC transfusions. These patients will undergo MRI of the liver to estimate liver iron content.
- •Patients with hepatic iron content of ≤ 7 mg Fe/ gm of liver will be included ii. Patients with hepatic iron content of ≥ 7 mg Fe/ gm of liver will undergo biopsy to look for absence of histological findings suggestive of cirrhosis, fibrosis and active hepatitis
- •h. Sickle nephropathy defined as Cr ≥ 1.5 times the ULN or biopsy proven i.Reversible SCD complication not ameliorated by hydroxyurea: i.Two or more vaso-occlusive crises requiring hospitalizations ii. Any episode of ACS while on hydroxyurea
- •Adequate physical function as measured by all of the following:
- •Karnofsky performance score > or equal to 70
- •Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by MUGA scan.
- •Pulmonary function: Pulse oximetry with a baseline O2 saturation of > 85%, DLCO > 40% (corrected for hemoglobin).
- •Renal function: Serum creatinine ≤ 1.5 x the upper limit of normal for age as per local laboratory and 24 hour urine creatinine clearance >70 mL/min/1.73 m2; or GFR > 70 mL/min/1.73 m2 by radionuclide GFR unless reason for transplant is sickle nephropathy
- •Hepatic function:
- •i. Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory; ii. ALT and AST < 5 times upper limit of normal. iii. Patients with hyperbilirubinemia because of hyper hemolysis, or who experience a sudden, profound change in the serum hemoglobin after a RBC transfusion are not excluded.
- •The HLA matched related donor must be willing to donate and must meet our institutional guidelines to donate peripheral blood stem cells
- •Absence of donor specific HLA antibodies.
- •Absence of clinical or radiographic evidence of neurologic event within 6 months prior to proceeding with transplantation.
- •Cerebral MRI/MRA within 6 months prior to initiation of transplant conditioning.
- •If patient has a neurologic event such as stroke or transient ischemic attack during recruitment process, patient will be deferred for 6 months before reconsideration.
- •Donor selection
- •Siblings who are ≥18 years and capable and willing to donate PBSC
- •Sibling donors are HLA-matched. HLA-A, B, C, and DRB1 match based on high-resolution typing
- •All sibling donors MUST meet institutional criteria for donation.
- •Donors with sickle cell trait (Hb AS) are permitted.
- •Donors with ABO minor incompatibility are permitted
排除标准
- •Patient selection
- •Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
- •Seropositivity for HIV.
- •Previous stem cell transplantation.
- •Participation in a clinical trial in which the patient received an investigational drug or device
- •A history of substance abuse as defined by version IV of the Diagnostic & Statistical Manual of Mental Disorders (DSM IV).
- •Demonstrated lack of compliance with prior medical care as determined by referring physician.
- •Pregnant or breast-feeding females.
- •Unwillingness to use approved contraception method from time of conditioning regimen and 4 months after discontinuation of all immunosuppressive medications.
- •Donor selection A. Inclusion Criteria
- •Siblings who are ≥18 years and capable and willing to donate PBSC
- •Sibling donors are HLA-matched. HLA-A, B, C, and DRB1 match based on high-resolution typing
- •All sibling donors MUST meet institutional criteria for donation.
- •Donors with sickle cell trait (Hb AS) are permitted.
- •Donors with ABO minor incompatibility are permitted
- •B. Exclusion Criteria
- •Donors with hemoglobinopathies: Hb SS, Hb SC, Hb Sβ0 and all other unstable hemoglobins
- •Presence of anti-donor HLA antibodies in the recipient
- •Donors with major ABO incompatibility are permitted
- •Donors who are HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
研究组 & 干预措施
Non Myeloablative regimen (Alemtuzumab)
Experimental
Sickle cell patient receives sibling donor peripheral blood stem cell transplant with non-myeloablative pre-transplant conditioning.
干预措施: Alemtuzumab (Drug)
Non Myeloablative regimen (Alemtuzumab)
Experimental
Sickle cell patient receives sibling donor peripheral blood stem cell transplant with non-myeloablative pre-transplant conditioning.
干预措施: Total Body Irradiation (Radiation)
Non Myeloablative regimen (Alemtuzumab)
Experimental
Sickle cell patient receives sibling donor peripheral blood stem cell transplant with non-myeloablative pre-transplant conditioning.
干预措施: Sirolimus (Drug)
结局指标
主要结局
Treatment Success
时间窗: up to 1 year after HSCT
Evaluating reversal of Hb S % to that of the donor's phenotype, in recipients of HLA matched-sibling peripheral blood - hematopoietic stem cell transplantation (HSCT) with NMA conditioning regimen. Testing for treatment success will include Hb Electrophoresis. Recipients with donors AA should have nearly 0% Hb S. Recipients with donors AS should have similar Hb S % (approximately \< 60%) as the donor. The proportion of patients experiencing treatment success, will be calculated with a 90% exact confidence interval.
次要结局
- Engraftment(up to 1 year after HSCT)
- Lymphocyte subsets(up to 2 years after HSCT)
- MDC, whole blood and CD3 Lineage(up to 1 year after HSCT)
- Probability of developing acute GVHD after HSCT.(up to 100 days after HSCT)
- Probability of developing chronic GVHD after HSCT.(up to 2 years after HSCT)
- Graft failure or Relapse(up to 2 years after HSCT)
- Discontinuation of Immunosuppressive therapy(up to 2 years after HSCT)
- Changes in the annual frequency of SCD-related hospitalization after(up to 2 years after HSCT)
- Sickle cell disease related organ damage(up to 2 years after HSCT)
- Quality of life measures(up to 2 years after HSCT)
- Opioid independence(up to 2 years after HSCT)
- Changes in monthly transfusions after HSCT(up to 2 years after HSCT)
- Transplant-related mortality(up to 2 years after HSCT)
研究者
Kathleen Dorritie
Principal Investigator
University of Pittsburgh
研究点 (1)
Loading locations...
相似试验
已完成
2 期
Modified Bone Marrow Stem Cell Transplantation for Chronic Myelogenous LeukemiaChronic Myeloid LeukemiaGraft vs Host DiseaseNCT00001144National Heart, Lung, and Blood Institute (NHLBI)50
已完成
1 期
Stem Cell (Modified Bone Marrow) Transplantation in HIV-Infected Patients With Blood CancerHematologic NeoplasmHIV InfectionNCT00005785National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)30
终止
2 期
Matched Unrelated Donor Transplant for Metastatic Renal Cell CarcinomaMetastatic Renal Cell CarcinomaNCT00318110Center for International Blood and Marrow Transplant Research4
Unknown
1 期
Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of Pancreatic CancerPancreatic Cancer Stage IIIPancreatic Cancer Stage IVNCT03236883Tianjin Medical University Cancer Institute and Hospital30
已完成
早期 1 期
Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic MalignanciesLymphocytic LeukemiaMixed Cell LeukemiaNon Hodgkin's LymphomaCMLALLLymphomaMyelodysplastic SyndromeAMLHodgkin LymphomaNCT00013533National Cancer Institute (NCI)30