search
Back to results

Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases

Primary Purpose

Autoimmune Disease, Neurologic Autoimmune Disease, Autologous Transplant Autoimmune

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Anti-Thymocyte Globulin
Autologous Hematopoietic Stem Cell Transplantation
Carmustine
Cytarabine
Etoposide
Laboratory Biomarker Analysis
Melphalan
Peripheral Blood Stem Cell Transplantation
Prednisone
Syngeneic Bone Marrow Transplantation
Sponsored by
Fred Hutchinson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autoimmune Disease focused on measuring 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

Eligibility Criteria

undefined - 71 Years (Child, Adult, Older Adult)All SexesDoes not accept 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
  • 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:

  • 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

Sites / Locations

  • Colorado Blood Cancer InstituteRecruiting
  • Fred Hutch/University of Washington Cancer ConsortiumRecruiting
  • Swedish Medical Center-First HillRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (immunosuppressive therapy followed by transplant)

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Transplant-related mortality
Defined as death within the first 100 days of transplant due to transplant-related complications.
Disease responses
Assessed by clinical, laboratory and radiologic evaluation
Engraftment kinetics
Monitored for engraftment kinetics of granulocytes, platelets and red cells 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
Efficacy of peripheral blood stem cell mobilization as evaluated by total number of harvested CD34+cells/kg, for autologous transplant.
Number of subjects with an exacerbation of autoimmune disease symptoms secondary to G-CSF (filgrastim) during peripheral blood stem cell mobilization
Subjects are evaluated by standardized clinical neurologic tests specific to autoimmune disease type.

Full Information

First Posted
July 15, 2008
Last Updated
September 14, 2023
Sponsor
Fred Hutchinson Cancer Center
search

1. Study Identification

Unique Protocol Identification Number
NCT00716066
Brief Title
Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases
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 Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 2008 (undefined)
Primary Completion Date
January 30, 2028 (Anticipated)
Study Completion Date
June 30, 2033 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fred Hutchinson Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (immunosuppressive therapy followed by transplant)
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
Anti-Thymocyte Globulin
Other Intervention Name(s)
Antithymocyte Globulin, Antithymocyte Serum, ATG, ATGAM, ATS, Thymoglobulin
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Autologous Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Autologous Stem Cell Transplantation
Intervention Description
Undergo autologous or syngeneic stem cell transplantation
Intervention Type
Drug
Intervention Name(s)
Carmustine
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
.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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213, 33419-42-0
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
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
Intervention Description
Given IV
Intervention Type
Procedure
Intervention Name(s)
Peripheral Blood Stem Cell Transplantation
Other Intervention Name(s)
PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplantation
Intervention Description
Undergo autologous or syngeneic stem cell transplantation
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
.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
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
Syngeneic Bone Marrow Transplantation
Intervention Description
Undergo syngeneic bone marrow transplantation
Primary Outcome Measure Information:
Title
Incidence of grades 4-5 regimen-related toxicity
Description
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.
Time Frame
Up to 1 year post-transplant
Secondary Outcome Measure Information:
Title
Transplant-related mortality
Description
Defined as death within the first 100 days of transplant due to transplant-related complications.
Time Frame
Within 100 days post-transplant
Title
Disease responses
Description
Assessed by clinical, laboratory and radiologic evaluation
Time Frame
Up to 5 years
Title
Engraftment kinetics
Description
Monitored for engraftment kinetics of granulocytes, platelets and red cells post-transplant.
Time Frame
Over first 60 days post-transplant
Title
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
Description
Efficacy of peripheral blood stem cell mobilization as evaluated by total number of harvested CD34+cells/kg, for autologous transplant.
Time Frame
Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations)
Title
Number of subjects with an exacerbation of autoimmune disease symptoms secondary to G-CSF (filgrastim) during peripheral blood stem cell mobilization
Description
Subjects are evaluated by standardized clinical neurologic tests specific to autoimmune disease type.
Time Frame
Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
71 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bernie McLaughlin
Phone
206.667-4916
Email
bmclaugh@fredhutch.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leona Holmberg
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Richard A. Nash
Phone
720-754-4800
Email
Richard.Nash@Healthonecares.com
First Name & Middle Initial & Last Name & Degree
Sarah Wright
Phone
303-577-6488
Email
sarah.wright@healthonecares.com
First Name & Middle Initial & Last Name & Degree
Richard A. Nash
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernie McLaughlin
Phone
206-667-4916
Email
bmclaugh@fredhutch.org
First Name & Middle Initial & Last Name & Degree
Leona Holmberg
Facility Name
Swedish Medical Center-First Hill
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122-4307
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernie McLaughlin
Phone
206-667-4916
Email
bmclaugh@fredhutch.org
First Name & Middle Initial & Last Name & Degree
James Bowen

12. IPD Sharing Statement

Learn more about this trial

Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases

We'll reach out to this number within 24 hrs