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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

Phase 2
70 Years
Open (Enrolling)
Autoimmune Disorder

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Trial Information

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


I. 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.


I. Evaluate disease responses and the duration of response to HDIT and autologous
hematopoietic stem cell transplantation (HSCT).

II. Determine the efficacy and safety of G-CSF (filgrastim) and prednisone or
cyclophosphamide for hematopoietic stem mobilization in patients with neurological
autoimmune diseases.


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.

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-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 disease as approve 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 stand 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

- Severe pulmonary dysfunction associated with a carbon monoxide diffusing capacity
(DLCO) (corrected for hemoglobin) < 40%, or requires supplemental oxygen

- 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 < 30ml/min/1.73 m^2 body surface area

- Serum glutamic pyruvic 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

- Patients with evidence of myelodysplasia

- Patients with a history of hypersensitivity to murine proteins

- Active malignancy (excluding localized squamous cell or basal cell carcinoma of the

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of grades 4-5 regimen-related toxicity as assessed by the Regimen Related Toxicity Scale

Outcome Description:

Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v.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.

Outcome Time Frame:

Within 28 days post-transplant

Safety Issue:


Principal Investigator

George Georges

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Institutional Review Board

Study ID:




Start Date:

June 2008

Completion Date:

Related Keywords:

  • Autoimmune Disorder
  • Autoimmune Diseases
  • Nervous System Diseases



Fred Hutchinson Cancer Research Center Seattle, Washington  98109
Swedish Neuroscience Institute Seattle, Washington  98122
Colorado Blood Cancer Institute Denver, Colorado  80218