A Phase II Trial of Non-Myeloablative Conditioning and Transplantation of Partially HLA-Mismatched/Haploidentical Related or Matched Unrelated Bone Marrow for Patients With Refractory Severe Aplastic Anemia and Other Bone Marrow Failure Syndromes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?
研究概览
简要总结
Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors.
详细描述
This research is being done to find out if bone marrow transplantation (BMT) followed by chemotherapy will help people with aplastic anemia who have failed other treatments.
You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow. Your disease has come back or not responded after receiving one or more immunosuppressive treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD) and graft failure have limited the survival for those people.
A small study done at Johns Hopkins has shown that in subjects with other diseases (blood cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects had complications of GVHD and engraftment failure.
People with aplastic anemia who have refractory disease (not responding to standard treatment) may join.
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
- — 至 73 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with relapsed or refractory SAA or very SAA defined:
- •Bone marrow (< 25% cellular)
- •Peripheral cytopenias (at least 2 of 3)
- •ANC < 500 per ml
- •Platelets < 20,000 per ml
- •Absolute retic < 60,000 or corrected retic < 1%
- •Very severe: as above, but ANC < 200
- •Disease may be designated as acquired or inherited if previous counts known (these other bone marrow failure disorders that are characterized by aplastic anemia may go by additional names such as dyskeratosis congenita or PNH)
- •Failed at least one course of immunosuppressive therapy (if presumed acquired disease). Patients with inherited disease will be characterized as refractory and do not require immunosuppressive first.
- •Age 0- upper age limit as determined by current institutional standards
- •Good performance status (ECOG 0 or 1; Karnofsky and Lansky 70-100)
- •Patients and donors must be able to sign consent forms (or if a minor the parent will sign). Donors should be willing to donate.
- •Patients must be geographically accessible and willing to participate in all stages of treatment.
- •Adequate end-organ function as measured by:
- •Left ventricular ejection fraction > or = to 35%, or shortening fraction > 25% (For pediatric patients, a normal ejection fraction is required)
- •Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST ≤ 5 x ULN
- •FEV1 and FVC > or = to 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation >92% on room air
排除标准
- •Patients will not be excluded on the basis of sex, racial or ethnic background.
- •Prior transfusions from selected donor (as this could have cause recipient alloimmunization against the donor)
- •Women of childbearing potential who currently are pregnant (HCG+) or who are not practicing adequate contraception.
- •Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up.
- •Uncontrolled viral, bacterial, or fungal infections (HIV infection permitted if viral load undetectable)
研究组 & 干预措施
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: Bone marrow transplant (Procedure)
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: Thymoglobulin (Drug)
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: Fludarabine (Drug)
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: Cyclophosphamide (Drug)
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: TBI (Radiation)
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: Mesna (Drug)
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: Tacrolimus (Drug)
Bone marrow transplant
Thymoglobulin on days -9 to -7 Fludarabine on days -6 to -2 Cyclophosphamide on days -6, -5, 3, 4 TBI on day -1 BMT on day 0 Mesna on days 3, 4 Tacrolimus on days 5-365 Mycophenolic acid mofetil on days 5-35
干预措施: Mycophenolic acid mofetil (Drug)
结局指标
主要结局
Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?
时间窗: 1 year
Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).
次要结局
- Number of Patients With Primary or Secondary Graft Failure Following Transplant(1 year)
- Participants With Chronic GVHD at One Year(1 year)
- Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant(1 year)
- Number of Patients That Have Survived at One Year(1 year)
- Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant(60 days)
- Number of Patients That Expired Due to Transplant Related Mortality(1 year)
- Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant(1 year)
- Number of Participants With Major Toxicities Related to Transplant(1 year)
- Participants That Were GVHD Free, Relapse Free Survival (GRFS)(1 year)
- Number of Participants With Grade II-IV or Grade III-IV Acute GVHD(1 year)