High-Dose Immunosuppressive Therapy Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) + Thymoglobulin Followed by Syngeneic or Autologous Hematopoietic Cell Transplantation for Patients With Autoimmune Neurologic Diseases
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 53
- 试验地点
- 3
- 主要终点
- Incidence of grades 4-5 regimen-related toxicity
研究概览
简要总结
This phase II trial studies the side effects and how well carmustine, etoposide, cytarabine and melphalan together with antithymocyte globulin before a stem cell transplant works in treating patients with autoimmune neurologic disease that did not respond to previous therapy. In autoimmune neurological diseases, the patient's own immune system 'attacks' the nervous system which might include the brain/spinal cord and/or the peripheral nerves. Giving high-dose chemotherapy, including carmustine, etoposide, cytarabine, melphalan, and antithymocyte globulin, before a stem cell transplant weakens the immune system and may help stop the immune system from 'attacking' a patient's nervous system. When the patient's own (autologous) stem cells are infused into the patient they help the bone marrow make red blood cells, white blood cells, and platelets so the blood counts can improve.
详细描述
OUTLINE:
Patients receive carmustine intravenously (IV) on day -6, etoposide IV and cytarabine IV twice daily (BID) on days -5 to -2, melphalan IV on day -1, and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone orally (PO) once daily (QD) on days 7-21, followed by 2 week taper.
After completion of study treatment, patients are followed up at 3 months, 1 year, and then annually thereafter for up to 5 years.
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 71 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with an autoimmune disorder of the central or peripheral nervous system will be eligible; this will include:
- •Primary Central Nervous System (CNS) vasculitis
- •Rasmussen's encephalitis
- •Autoimmune peripheral neuropathy (anti-Hu [Anna-1], anti-GM1 [GD1b], anti-MAG, anti-ganglioside, anti-sulfatide)
- •Autoimmune cerebellar degeneration
- •Gait Ataxia with Late age Onset Polyneuropathy (GALOP)
- •Stiff Person Syndrome
- •Chronic Inflammatory Demyelinating Polyneuropathy
- •Myasthenia Gravis
- •Lambert-Eaton myasthenic syndrome
- •Human T-cell lymphotropic virus (HTLV)-1-associated myelopathy (HAM) / tropical spastic paraparesis (TSP)
- •Opsoclonus/myoclonus (anti-Ri)
- •Neuromyelitis optica
- •Multiple sclerosis
- •Other central or peripheral nervous system autoimmune diseases as approved by study neurologists and the Fred Hutchinson Cancer Research Center (FHCRC) faculty at Patient Care Conference (PCC)
- •Patients must satisfy the criteria for a diagnosis of one of the severe neurological autoimmune disorders outlined
- •Patients age =< 70 years
- •Evidence of disease activity as outlined (e.g. gadolinium enhancement on magnetic resonance imaging of the brain or clinical progression)
- •Patients must have failed at least 2 lines of standard therapy as outlined for the specific diseases
- •DONOR: Sibling of any patient enrolled on this protocol proven by ABO typing, human leukocyte antigen (HLA) typing and variable number tandem repeat (VNTR) analysis to be syngeneic with the patient (e.g. identical twin)
- •DONOR: Willing to undergo multiple apheresis procedures (except donors < 12 years who will undergo bone marrow harvests)
排除标准
- •Age >= 71 years
- •Pregnancy or expressed plans to become pregnant within 1 year of the procedure
- •Patients who are serologically positive for human immunodeficiency virus (HIV)
- •Patients with pulmonary, cardiac, hepatic or renal impairment that would limit their ability to receive cytoreductive therapy and compromise their survival; this should include patients with any of the following:
- •Severe pulmonary dysfunction associated with a carbon monoxide diffusing capacity (DLCO) (corrected for hemoglobin) < 60%, or requires supplemental oxygen; patients who are unable to perform pulmonary function test (because of underlying disease) will be excluded if the oxygen saturation is < 92% on room air
- •Uncontrolled malignant arrhythmias, or clinical evidence of congestive heart failure (New York class III-IV) or ejection fraction < 50%
- •Renal disease with estimated glomerular filtration rate (GFR) by creatinine clearance or iothalamate clearance < 50 ml/min/1.73 m^2 body surface area
- •Serum glutamate pyruvate transaminase (SGPT)/aspartate aminotransferase (AST) > 3 times normal or direct bilirubin greater than 2.5 mg/dL on two repeated tests
- •Active uncontrolled infection
- •Demonstrated lack of compliance with prior medical care
- •Patients whose life expectancy is limited by illness other than their neurological condition
- •Patients with evidence of myelodysplasia
- •Active malignancy (excluding localized squamous cell or basal cell carcinoma of the skin)
- •DONOR: Inadequate documentation that donor and recipient are syngeneic
- •DONOR: Donors who do not fulfill criteria as apheresis donors as established by institutional guidelines
- •DONOR: Concordant for autoimmune neurological disease(s) as determined by neurological evaluation
研究组 & 干预措施
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Anti-Thymocyte Globulin (Biological)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Carmustine (Drug)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Melphalan (Drug)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Cytarabine (Drug)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Etoposide (Drug)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Prednisone (Drug)
Treatment (immunosuppressive therapy followed by transplant)
Patients receive carmustine IV on day -6, etoposide IV and cytarabine IV BID on days -5 to -2, melphalan IV on day -1 and antithymocyte globulin IV on days -2 and -1. Patients then undergo autologous or syngeneic stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
干预措施: Syngeneic Bone Marrow Transplantation (Procedure)
结局指标
主要结局
Incidence of grades 4-5 regimen-related toxicity
时间窗: Up to 1 year post-transplant
Assessed by the Regimen Related Toxicity Scale. Using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The development of a grade 4 to 5 toxicity of any of the included major organ systems within the first 365 days after transplant will be defined as regimen-related toxicity.
次要结局
- Transplant-related mortality(Within 100 days post-transplant)
- Disease responses(Up to 5 years)
- Engraftment kinetics(Over first 60 days post-transplant)
- Number of subjects achieving greater than or equal to 4.0 x 10^6 CD34+ cells/kg, after up to two peripheral blood stem cell mobilizations(Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations))
- Number of subjects with an exacerbation of autoimmune disease symptoms secondary to G-CSF (filgrastim) during peripheral blood stem cell mobilization(Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations))