Allogeneic Stem Cell Transplantation for Patients With Severe Aplastic Anemia, Using Matched Unrelated Donors and Mismatched Related Donors (SAA MUD)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Number of Subjects Alive at 100 Days Post Transplant
研究概览
简要总结
Patients have been diagnosed with severe Aplastic Anemia that have not responded to treatment with immunosuppressive therapy (drugs that suppress the immune system, for example Steroids). The immune system is the system in the body that helps protect the body and fights bacterial, viral and fungal infections.
Research studies have shown that patients with Aplastic Anemia have improved survival (may live longer) after receiving a HLA (Human Leukocyte Antigen) identical sibling (brother and sister) stem cell transplants. Patients who do not have matched siblings can undergo immunosuppressive therapy, which has also shown to improve outcome. Unfortunately patients who do not respond to immunosuppressive therapy usually die. The best chance of survival for these patients is an HLA matched unrelated or mismatched related stem cell transplant as described below.
Stem cells are created in the bone marrow. They mature into different types of blood cells that people need including red blood cells which carry oxygen around the body, white blood cells which help fight infections, and platelets which help the blood to clot and prevent bleeding. For a matched unrelated stem cell transplant, stem cells are collected from a person (donor) who is not related to the patient but who has the same type of stem cells. For a mismatched related stem cell transplant, stem cells are collected from a donor who is related to the patient and whose stem cells are almost the same as those of the patient but not exactly. The patient then receives high dose chemotherapy. This chemotherapy kills the stem cells in the patient's bone marrow. Stem cells that have been collected from the donor are then given to the patient to replace the stem cells that have been killed.
The major problems associated with these types of stem cell transplants are graft rejection (where the patient's immune system rejects the donor stem cells) and severe graft versus host disease (GVHD), where the donors stem cell reacts against the patient's tissues in the body.
详细描述
Before patients receive any treatments, they will have the following:
- Complete history and physical exam
- Dental consultation
- Bone marrow aspirate
- Blood tests
- Urinanalysis
- Tests to look at your lungs (Chest X-ray and PFT's and DLCO)
- Tests to look at your heart (EKG, MUGA, or echocardiogram)
- Pregnancy test for females of childbearing age.
Once the decision has been made by the patients to have a mismatched related or matched unrelated stem cell transplant, the patient will receive treatment called a "conditioning regimen" to prepare their body for the transplant. The purpose of this conditioning regimen is to kill the stem cells in the bone marrow, so that the patients immune system is suppressed (lowered or stopped from working), so their body will not reject the donors stem cells (transplant).
The medicines which will be given as part of the conditioning regimen include Cyclophosphamide (Cytoxan) and Campath 1H. Both of these medications are approved by the Food and Drug Administration. Cyclophosphamide will be given for four days in a row. Cyclophosphamide is broken down into different chemicals and removed from the body in the urine. These different chemicals can cause bleeding in the bladder. Mesna is a drug that will be given with Cytoxan to prevent the build up of these chemicals that cause bleeding from the bladder. Campath 1H will also be given for four days. After the medicines, the patient will receive total body irradiation (TBI). Total body irradiation is strong doses of radiation (like x-rays) given to almost the whole body. One dose of TBI will be given to patients receiving a matched stem cell infusion while two doses of TBI will be given to patients receiving a mismatch stem cell infusion. After the conditioning regimen, the patient will then receive the stem cells (transplant). These stem cells will be given as an infusion (drip) into a vein.
Patients will receive the drugs Tacrolimus (FK506) and Methotrexate to help prevent the complication of graft versus host disease. Methotrexate will be given on days 1, 3, 6 and 11 after they receive the stem cells. During this time, the patient will be on the stem cell transplant unit in protective isolation to help protect from developing infections.
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
- 1 Minute 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Severe Aplastic Anemia (SAA) based on bone marrow aspirate and biopsy results.
- •Failure to respond to immunosuppressive therapy.
- •Lack of an Human Leukocyte Antigen (HLA) identical family member.
- •A 6/6 or 5/6 HLA matched unrelated donor or a 5/6 matched related donor available after high resolution HLA typing.
- •Age from birth to 60 years.
排除标准
- •Severe disease other than aplastic anemia that would limit the probability of survival during the graft procedure. Patients who present with active infection must be treated to maximally resolve this problem before beginning the conditioning regimen.
- •Human immunodeficiency virus (HIV) seropositive patients
- •Patients who have clonal cytogenetic abnormalities or a myelodysplastic syndrome.
- •Patient greater than 60 years of age.
- •Women who are pregnant or nursing.
- •Patients with active hepatitis
- •Patients with severe cardiac dysfunction defined as shortening fraction < 25%.
- •Patients with severe renal dysfunction defined as creatinine clearance < 40 ml/mim/1.73m
- •Patient with severe pulmonary dysfunction with forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO) 40% of predicted or 3 standard deviations (SD) below normal.
研究组 & 干预措施
Patients
Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.
Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion
干预措施: Cytoxan (Drug)
Patients
Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.
Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion
干预措施: Campath (Drug)
Patients
Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.
Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion
干预措施: Total Body Irradiation (TBI) (Radiation)
Patients
Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.
Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion
干预措施: FK-506 (Drug)
Patients
Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.
Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion
干预措施: Methotrexate (Drug)
Patients
Patients with a diagnosis of severe aplastic anemia who require an allogeneic stem cell transplant but lack an Human Leukocyte Antigen (HLA) identical family member.
Cytoxan, Campath, TBI-Total Body Irradiation, FK-506, Methotrexate, Stem Cell Infusion
干预措施: Stem cell infusion (Procedure)
结局指标
主要结局
Number of Subjects Alive at 100 Days Post Transplant
时间窗: 100 days
次要结局
- Number of Patients With Engraftment Rate at 100 Days Post Transplant(100 days post transplant)
- Number of Patients With Acute GVHD at 100 Days Post Transplant(100 days)
- Number of Patients With Chronic GVHD at 2 Years Post Transplant(2 years)
- Number of Subjects Alive at 1 Year Post Transplant(1 year)
- Number of Subjects Alive at 2 Years Post Transplant(2 years)
研究者
Kathryn Leung
Principal Investigator
Baylor College of Medicine