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