Autoimmune Disease | Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases

Autoimmune Disease research study

What is the primary objective of this study?

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.

Who is eligible to participate?

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 (only patients with relapsing/remitting multiple sclerosis [MS] will be included) - 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 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; 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 - 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

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Autoimmune Disease

Neurologic Autoimmune Disease

Autologous Transplant Autoimmune

Multiple Sclerosis Transplant

MS Stem Cell Transplant

Multiple Sclerosis Stem Cell Transplant

Stiff Person Syndrome

HCT for Neurologic Autoimmune Disorders

CIDP Transplant

Myasthenia Gravis Transplant

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Biological:Anti-Thymocyte GlobulinGiven IV

Procedure:Autologous Hematopoietic Stem Cell TransplantationUndergo autologous or syngeneic peripheral blood stem cell transplantation

Drug:CarmustineGiven IV

Drug:CytarabineGiven IV

Drug:EtoposideGiven IV

Other:Laboratory Biomarker AnalysisCorrelative studies

Drug:MelphalanGiven IV

Procedure:Peripheral Blood Stem Cell TransplantationUndergo autologous or syngeneic peripheral blood stem cell transplantation

Drug:PrednisoneGiven PO

Procedure:Syngeneic Bone Marrow TransplantationUndergo syngeneic bone marrow transplantation

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

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 peripheral blood stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.

Study Status


Start Date: June 2008

Completed Date: December 1, 2021

Phase: Phase 2

Type: Interventional


Primary Outcome: Incidence of grades 4-5 regimen-related toxicity

Secondary Outcome: Disease responses

Study sponsors, principal investigator, and references

Principal Investigator: George Georges

Lead Sponsor: Fred Hutchinson Cancer Research Center

Collaborator: National Cancer Institute (NCI)

More information:

Discuss Etoposide