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Carmustine, Etoposide, Cytarabine, Melphalan, and Antithymocyte Globulin Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Autoimmune Neurologic Disease That Did Not Respond to Previous Therapy

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Autoimmune Disorder

Intervention: anti-thymocyte globulin (Biological); carmustine (Drug); cytarabine (Drug); etoposide (Drug); melphalan (Drug); prednisone (Drug); autologous hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure); syngeneic bone marrow transplantation (Procedure); laboratory biomarker analysis (Other)

Phase: Phase 2

Status: Recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
George Georges, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


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.

Clinical Details

Official 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

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

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

Secondary outcome:

Transplant-related mortality

Disease responses as assessed by clinical, laboratory and radiologic evaluation

Engraftment kinetics

Efficacy of peripheral blood stem cell mobilization from syngeneic donors and autograft recipients

Detailed description: PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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. 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 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.


Minimum age: N/A. Maximum age: 70 Years. Gender(s): Both.


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 (CIDP)

- 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

- 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) < 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 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


- Patients with evidence of myelodysplasia

- 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

Locations and Contacts

Colorado Blood Cancer Institute, Denver, Colorado 80218, United States; Recruiting
Richard A. Nash, Phone: 720-754-4800
Richard A. Nash, Principal Investigator

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States; Recruiting
George E. Georges, Phone: 206-667-6886
George E. Georges, Principal Investigator

Swedish Neuroscience Institute, Seattle, Washington 98122, United States; Recruiting
James Bowen, Phone: 206-320-2200
James Bowen, Principal Investigator

Additional Information

Starting date: June 2008
Last updated: March 11, 2015

Page last updated: August 23, 2015

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