Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases

Title: 
Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases
Recruitment Status: 
Status Last Updated: 
June 11, 2020
Study Purpose: 

This phase II trial studies the side effects and how well carmustine, etoposide, cytarabine and melphalan together with antithymocyte globulin before a peripheral blood 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 peripheral blood 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.

Intervention/Treatment: 
Procedure: Autologous Hematopoietic Stem Cell Transplantation, Drug: Carmustine Drug: Cytarabine, Drug: Etoposide,
Phase: 
Study Description: 

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 peripheral blood 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.

Study Type: 
Official Title: 
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
Study Start Date: 
June 2008
Study Completion Date: 
December 1, 2027
Primary Objective(s): 
  • Evaluate the safety of high-dose carmustine, etoposide, Ara-c (cytarabine) and melphalan (BEAM) and Thymoglobulin (antithymocyte globulin) as a high-dose immunosuppressive treatment (HDIT) regimen in patients with severe, refractory neurological autoimmune disease.
  • Incidence of grades 4-5 regimen-related toxicity [ Time Frame: Within 28 days 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 28 days after transplant will be defined as regimen-related toxicity.
Secondary Objective(s): 
  • Evaluate disease responses and the duration of response to HDIT and autologous hematopoietic stem cell transplantation (HSCT).
  • Determine the efficacy and safety of G-CSF (filgrastim) and prednisone or cyclophosphamide for hematopoietic stem mobilization in patients with neurological autoimmune diseases.
  • Disease responses [ Time Frame: Up to 5 years ]
  • Assessed by clinical, laboratory and radiologic evaluation
  • Engraftment kinetics [ Time Frame: Over first 60 days post-transplant ]
  • Monitored for engraftment kinetics of granulocytes, platelets and red cells 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 [ Time Frame: Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations) ]
  • Efficacy of peripheral blood stem cell mobilization as evaluated by total number of harvested CD34+cells/kg, for autologous transplant.
  • Number of subjects with an exacerbation of autoimmune disease symptoms secondary to G-CSF (filgrastim) during peripheral blood stem cell mobilization [ Time Frame: Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations) ]
  • Subjects are evaluated by standardized clinical neurologic tests specific to autoimmune disease type.
  • Transplant-related mortality [ Time Frame: Within 100 days post-transplant ]
  • Defined as death within the first 100 days of transplant due to transplant-related complications.
Eligibility: 

Ages Eligible for Study: up to 71 Years   (Child, Adult, Older Adult)

Sexes Eligible for Study: All

Accepts Healthy Volunteers: No

Inclusion Criteria: 
  • 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
  • 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)
Exclusion Criteria: 
  • 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
Study Site(s)/Location(s): 

United States, Colorado

Colorado Blood Cancer Institute    Recruiting

Denver, Colorado, United States, 80218

Contact: Richard A. Nash    720-754-4800    Richard.Nash@Healthonecares.com   

Principal Investigator: Richard A. Nash         



United States, Washington

Fred Hutch/University of Washington Cancer Consortium    Recruiting

Seattle, Washington, United States, 98109

Contact: Bernie McLaughlin    206-667-4916    bmclaugh@fredhutch.org   

Principal Investigator: George E. Georges         

Swedish Medical Center-First Hill    Recruiting

Seattle, Washington, United States, 98122-4307

Contact: Bernie McLaughlin    206-667-4916    bmclaugh@fredhutch.org   

Principal Investigator: James Bowen     

Sponsors & Collaborators: 

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Principal Investigator(s): 

Principal Investigator:

George Georges

Fred Hutch/University of Washington Cancer Consortium

For more information, please contact the Study Coordinator: 

Contact:  

Email: 

Phone: 

ClinicalTrials.gov ID: 
NCT00716066