Allogeneic Bone Marrow Transplantation From HLA Identical Related Donors for Patients With Hemoglobinopathies: Hemoglobin SS, Hemoglobin SC, or Hemoglobin SB0/+ Thalassemia
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Number of Participants Evaluated for Evidence of Recovery of Organ Function Measured Via MRI or PET Scan.
研究概览
简要总结
Patients are being asked to participate in this study because they have severe sickle cell anemia (SCD) with or without the beta thalassemia trait. Sickle cell anemia is an illness where the red blood cells change shape and can clog up blood vessels. This keeps the body from getting the oxygen it needs. Thalassemia is when the body does not make enough hemoglobin, something that helps the oxygen get to the places it needs to go in the body. The patient may or may not need to get regular blood transfusions (getting more blood) to improve their quality of life (feel better) and prevent organ damage (problems with the brain, heart, lung, kidney, and gonad, for example.). The transfusions can also cause problems, including iron overload (too much iron in the blood), which can be fatal (patients can die) without regular deferoxamine shots. Even with the best usual treatments, people with thalassemia or SCD die sooner. There is no proven cure.
We would like to treat patients using bone marrow transplantation, a treatment that has been used for people with SCD. The transplant uses healthy "matched" bone marrow. This comes from a brother or sister who does not have sickle cell disease or severe thalassemia. If the treatment works, the sickle cell disease or thalassemia may be cured. This treatment has been used to treat patients with sickle cell disease or thalassemia. It has worked in most cases. We hope, but cannot promise, that the transplanted marrow will make healthy cells, and patients will not have sickle cell disease or severe thalassemia anymore.
We do not know what effect this treatment will have on the damage that has already been done by the disease. Finding that out is the main reason for this study. Currently, very little has been reported about organ function after bone marrow transplants in patients with sickle cell anemia.
详细描述
Prior to any bone marrow transplant, we will need patients to:
- Answer questions about their medical history;
- Undergo a physical examination;
- Have tests done to see how well the lungs are working;
- Have a chest x-ray;
- Have an EKG to look at the heart;
- Have an MRI & MRA (Magnetic Resonance Angiography, which looks at the blood vessels and the blood flowing through them). These 2 tests will look to see if the patient has had any strokes;
- Have a PET scan to look at the head and body;
- Have a liver biopsy to determine if the liver has been damaged (which can happen from iron overload that happens after many transfusions). Too much liver damage would mean a transplant cannot be done.
For the liver biopsy, the skin is numbed with medicine, and a special needle goes into the liver. The needle removes a very small piece of the liver (tissue). The tissue is taken and examined.
Also, about 30 cc (2 tablespoons) of blood will be drawn to test the blood for viruses, including HIV (the virus that causes AIDS). If the HIV test is positive, a transplant will not be done because it would be too dangerous for the patient.
At least 2 weeks before the bone marrow infusion, the patient will be immunized with Prevnar 7. Prevnar 7 is a vaccine that is used in children to protect against some types of bacteria called Streptococcus pneumoniae, which can cause the lung infection called pneumonia. People with Sickle Cell anemia are at a higher risk of dying from an infection from this type of bacteria. Although children are regularly given the Prevnar 7 vaccine, it is not common to test a child's immune response to the vaccine. In this study, we will check the immune system's response to the vaccine by drawing an extra 3 mL (less than 1 teaspoon) of blood 3 weeks after the patient gets the Prevnar 7 vaccine.
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 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a related HLA genotype identical donor and hemoglobin SS, hemoglobin SC, or hemoglobin Sb0/+ and at least one of the following conditions:
- •Previous central nervous system vaso-occlusive episode with or without residual neurologic findings, or has an abnormal transcranial doppler exam without neurologic findings, or abnormal MRI/MRA of the brain with or without neurologic findings;
- •Frequent painful vaso-occlusive episodes which significantly interfere with normal life activities and which necessitate chronic transfusion therapy;
- •Recurrent SCD chest syndrome events, which necessitate chronic transfusion therapy;
- •Severe anemia which prevents acceptable quality of life and necessitates chronic transfusion therapy;
- •Any of the above symptoms in which the patient is not undergoing chronic transfusion therapy;
- •The patient is undergoing chronic transfusion therapy for symptoms other than those listed and which significantly interferes with normal life activities;
- •Failed hydroxyurea therapy;
- •Indication of pulmonary hypertension on 2 separate echocardiogram examinations;
- •Patients who plan to return to resource poor areas/countries.
- •Between the ages of birth and 40 years.
- •Women of childbearing potential must have a negative pregnancy test.
- •EXCLUSION CRITERIA:
- •Patient with biopsy proven chronic active hepatitis or fibrosis with portal bridging.
- •Patient with SCD chronic lung disease > stage 3 (see Appendix 1).
- •Patient with severe renal dysfunction defined as creatinine clearance < 40 mL/min/1.73 M^
- •Patient with severe cardiac dysfunction defined as echocardiogram shortening fraction < 25% or NYHA class III or IV.
- •Patient with HIV infection.
- •Patient with unspecified chronic toxicity serious enough to detrimentally affect the patient's capacity to tolerate bone marrow transplantation.
- •Patient or patient's guardian(s) unable to understand the nature and risks inherent in the BMT process.
- •Pregnant/lactating women and those unwilling to use acceptable contraception will be excluded.
- •Patient or patient's guardian who have not signed an informed consent.
- •NOTE: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CAGT Protocol Review Committee and the FDA reviewer.
排除标准
- 未提供
研究组 & 干预措施
Allogeneic BMT/SCT Transplant
Busulfan, Campath 1H, Cyclophosphamide and MESNA:
Bone marrow infusion with pre-meds as per SOPs to take place on Day 0.
Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest.
干预措施: Busulfan (Drug)
Allogeneic BMT/SCT Transplant
Busulfan, Campath 1H, Cyclophosphamide and MESNA:
Bone marrow infusion with pre-meds as per SOPs to take place on Day 0.
Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest.
干预措施: Campath 1H (Biological)
Allogeneic BMT/SCT Transplant
Busulfan, Campath 1H, Cyclophosphamide and MESNA:
Bone marrow infusion with pre-meds as per SOPs to take place on Day 0.
Bone marrow dose: To ensure the probability for bone marrow engraftment, 4 x 10^8 nucleated cells/kg patient weight will be the target at donor bone marrow harvest.
干预措施: Cyclophosphamide and MESNA (Drug)
结局指标
主要结局
Number of Participants Evaluated for Evidence of Recovery of Organ Function Measured Via MRI or PET Scan.
时间窗: One year
Assess Number of participants that recovered organ function diagnosed with sickle cell disease (SCD) or sickle hemoglobin variants after undergoing allogeneic SCT/BMT from HLA genotype identical donors.
Number of Participants With Pre and Post Transplant PET Scan to Assess Organ Recovery Based on Rate of Acquisition.
时间窗: One year
Number of participants that did or did not have pre- and post- PET scans.
Number of Participants With Immune Response to Immunization After BMT in Participants With SCD, Hemoglobin SC, or Hemoglobin Sb0/+.
时间窗: up to 12 months
Vaccine response will be measured via a humoral immunity panel evaluating streptococcus pneumonia IgG antibodies (microgram/mL). Panels are obtained pre and 1+ month post vaccination. Standard recommendations define a normal responder as having \>4 fold increase in antibody level in 50-70% of the serotypes found in the vaccine.
次要结局
未报告次要终点
研究者
Tami D. John
Assistant Professor, Pediatrics-Hema & Oncology
Baylor College of Medicine