Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases

Fred Hutchinson Cancer Center (FHCC)

Status and phase

Active, not recruiting

Phase 2

Conditions

Rasmussen Subacute Encephalitis

Chronic Inflammatory Demyelinating Polyneuropathy

Cerebellar Degeneration

Autoimmune Disease

Autoimmune Nervous System Disorder

MS Stem Cell Transplant

Autologous Transplant Autoimmune

Central Nervous System Vasculitis

Myasthenia Gravis Transplant

Multiple Sclerosis Stem Cell Transplant

Myasthenia Gravis

CIDP Transplant

Neuromyelitis Optica

Lambert Eaton Myasthenic Syndrome

Neurologic Autoimmune Disease

Opsoclonus Myoclonus Syndrome

Stiff Person Syndrome

Multiple Sclerosis Transplant

HCT for Neurologic Autoimmune Disorders

Treatments

Drug: Cytarabine

Biological: Anti-Thymocyte Globulin

Procedure: Peripheral Blood Stem Cell Transplantation

Procedure: Autologous Hematopoietic Stem Cell Transplantation

Drug: Prednisone

Other: Laboratory Biomarker Analysis

Drug: Carmustine

Drug: Melphalan

Procedure: Syngeneic Bone Marrow Transplantation

Drug: Etoposide

Study type

Interventional

Funder types

Other

Identifiers

NCT00716066

NCI-2010-00403 (Registry Identifier)

2260.00 (Other Identifier)

RG9213030 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

53 patients

Sex

All

Ages

Under 71 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

53 participants in 1 patient group

Treatment (immunosuppressive therapy followed by transplant)

Experimental group

Description:

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.

Treatment: