Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases

• Register: ClinicalTrials.gov
• Last refreshed on: 12 February 2024
• Main ID: NCT00716066
• Date of registration: 15/07/2008
• Prospective Registration: No
• Primary sponsor: Fred Hutchinson Cancer Center
• Public title: Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases
• Scientific 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
• Date of first enrolment: June 2008
• Target sample size: 53
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT00716066
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Leona Holmberg
• Affiliation: Fred Hutch/University of Washington Cancer Consortium

Key inclusion & exclusion criteria

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

- 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)

Exclusion Criteria:

- 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



Age minimum: N/A
Age maximum: 71 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myasthenia Gravis Transplant

Rasmussen Subacute Encephalitis

CIDP Transplant

Neurologic Autoimmune Disease

Neuromyelitis Optica

Cerebellar Degeneration

Central Nervous System Vasculitis

Lambert Eaton Myasthenic Syndrome

MS Stem Cell Transplant

Myasthenia Gravis

Stiff Person Syndrome

Autoimmune Disease

HCT for Neurologic Autoimmune Disorders

Autologous Transplant Autoimmune

Multiple Sclerosis Stem Cell Transplant

Autoimmune Nervous System Disorder

Chronic Inflammatory Demyelinating Polyneuropathy

Multiple Sclerosis Transplant

Opsoclonus Myoclonus Syndrome

Intervention(s)

Biological: Anti-Thymocyte Globulin

Procedure: Syngeneic Bone Marrow Transplantation

Drug: Melphalan

Procedure: Autologous Hematopoietic Stem Cell Transplantation

Procedure: Peripheral Blood Stem Cell Transplantation

Drug: Etoposide

Drug: Cytarabine

Other: Laboratory Biomarker Analysis

Drug: Carmustine

Drug: Prednisone

Primary Outcome(s)

Incidence of grades 4-5 regimen-related toxicity [Time Frame: Up to 1 year post-transplant]

Secondary Outcome(s)

Engraftment kinetics [Time Frame: Over first 60 days post-transplant]

Disease responses [Time Frame: Up to 5 years]

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)]

Transplant-related mortality [Time Frame: Within 100 days post-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)]

Secondary ID(s)

2260.00

NCI-2010-00403

RG9213030

Source(s) of Monetary Support

Please refer to primary and secondary sponsors