Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases

NCT00716066 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: 2260.00NCI-2010-00403RG9213030
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

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; Autoimmune Nervous System Disorder; Central Nervous System Vasculitis; Cerebellar Degeneration; Chronic Inflammatory Demyelinating Polyneuropathy; Lambert Eaton Myasthenic Syndrome; Myasthenia Gravis; Neuromyelitis Optica; Opsoclonus Myoclonus Syndrome; Rasmussen Subacute Encephalitis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of grades 4-5 regimen-related toxicity

  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 365 days after transplant will be defined as regimen-related toxicity.

  Up to 1 year post-transplant

Secondary Outcomes (5)

• Transplant-related mortality

  Within 100 days post-transplant

• Disease responses

  Up to 5 years

• Engraftment kinetics

  Over first 60 days 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

  Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations)

• Number of subjects with an exacerbation of autoimmune disease symptoms secondary to G-CSF (filgrastim) during peripheral blood stem cell mobilization

  Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations)

Study Arms (1)

Treatment (immunosuppressive therapy followed by transplant)

EXPERIMENTAL

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.

Biological: Anti-Thymocyte Globulin; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Prednisone; Procedure: Syngeneic Bone Marrow Transplantation

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous or syngeneic stem cell transplantation

Also known as: Autologous Stem Cell Transplantation

Treatment (immunosuppressive therapy followed by transplant)

Cytarabine DRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453, 147-94-4

Treatment (immunosuppressive therapy followed by transplant)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213, 33419-42-0

Treatment (immunosuppressive therapy followed by transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (immunosuppressive therapy followed by transplant)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813, 148-82-3

Treatment (immunosuppressive therapy followed by transplant)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous or syngeneic stem cell transplantation

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation

Treatment (immunosuppressive therapy followed by transplant)

Prednisone DRUG

Given PO

Also known as: .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone, 53-03-2

Treatment (immunosuppressive therapy followed by transplant)

Syngeneic Bone Marrow Transplantation PROCEDURE

Undergo syngeneic bone marrow transplantation

Treatment (immunosuppressive therapy followed by transplant)

Anti-Thymocyte Globulin BIOLOGICAL

Given IV

Also known as: Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin

Treatment (immunosuppressive therapy followed by transplant)

Carmustine DRUG

Given IV

Also known as: BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, Gliadel, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021, 154-93-8

Treatment (immunosuppressive therapy followed by transplant)

Eligibility Criteria

• Age: Up to 71 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead

Study Sites (3)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Swedish Medical Center-First Hill

Seattle, Washington, 98122-4307, United States

Location

MeSH Terms

Conditions

Autoimmune Diseases; Autoimmune Diseases of the Nervous System; Stiff-Person Syndrome; Vasculitis, Central Nervous System; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Lambert-Eaton Myasthenic Syndrome; Myasthenia Gravis; Neuromyelitis Optica; Opsoclonus-Myoclonus Syndrome; Rasmussen subacute encephalitis

Interventions

Antilymphocyte Serum; thymoglobulin; Carmustine; carmustine, poliferprosan 20 drug combination; Cytarabine; Etoposide; Melphalan; Peripheral Blood Stem Cell Transplantation; Prednisone; deltacortene; prednylidene

Condition Hierarchy (Ancestors)

Immune System Diseases; Nervous System Diseases; Spinal Cord Diseases; Central Nervous System Diseases; Neuromuscular Diseases; Cerebrovascular Disorders; Brain Diseases; Vascular Diseases; Cardiovascular Diseases; Vasculitis; Polyradiculoneuropathy; Demyelinating Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases; Ocular Motility Disorders; Myoclonus; Dyskinesias; Neurologic Manifestations

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Leona Holmberg

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2008
• First Posted: July 16, 2008
• Study Start: June 1, 2008
• Primary Completion: December 30, 2025
• Study Completion (Estimated): January 31, 2030
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (3)