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Trial record 33 of 75 for:    multiple sclerosis stem cell

Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases

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ClinicalTrials.gov Identifier: NCT00716066
Recruitment Status : Recruiting
First Posted : July 16, 2008
Last Update Posted : August 27, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE July 15, 2008
First Posted Date  ICMJE July 16, 2008
Last Update Posted Date August 27, 2019
Study Start Date  ICMJE June 2008
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
Incidence of grades 4-5 regimen-related toxicity [ Time Frame: Within 28 days post-transplant ]
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 28 days after transplant will be defined as regimen-related toxicity.
Original Primary Outcome Measures  ICMJE
 (submitted: July 15, 2008)
  • Incidence of grades 4-5 regimen-related toxicity
  • Incidence of severe transplant-related complications
  • Transplant-related mortality
  • Early disease progression
  • Loss of neurological function
Change History Complete list of historical versions of study NCT00716066 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2019)
  • Disease responses [ Time Frame: Up to 5 years ]
    Assessed by clinical, laboratory and radiologic evaluation
  • Engraftment kinetics [ Time Frame: Over first 60 days post-transplant ]
    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 [ Time Frame: Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two 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 [ Time Frame: Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations) ]
    Subjects are evaluated by standardized clinical neurologic tests specific to autoimmune disease type.
  • Transplant-related mortality [ Time Frame: Within 100 days post-transplant ]
    Defined as death within the first 100 days of transplant due to transplant-related complications.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 15, 2008)
  • Disease response as assessed by clinical, laboratory, and radiologic evaluation
  • Engraftment kinetics
  • Efficacy of peripheral blood stem cell mobilization from syngeneic donors and autograft recipients
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases
Official Title  ICMJE 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
Brief 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Biological: Anti-Thymocyte Globulin
    Given IV
    Other Names:
    • Antithymocyte Globulin
    • Antithymocyte Serum
    • ATG
    • ATGAM
    • ATS
    • Thymoglobulin
  • Procedure: Autologous Hematopoietic Stem Cell Transplantation
    Undergo autologous or syngeneic peripheral blood stem cell transplantation
    Other Name: Autologous Stem Cell Transplantation
  • Drug: Carmustine
    Given IV
    Other Names:
    • 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
  • Drug: Cytarabine
    Given IV
    Other Names:
    • .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
  • Drug: Etoposide
    Given IV
    Other Names:
    • Demethyl Epipodophyllotoxin Ethylidine Glucoside
    • EPEG
    • Lastet
    • Toposar
    • Vepesid
    • VP 16-213
    • VP-16
    • VP-16-213
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Melphalan
    Given IV
    Other Names:
    • 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
  • Procedure: Peripheral Blood Stem Cell Transplantation
    Undergo autologous or syngeneic peripheral blood stem cell transplantation
    Other Names:
    • PBPC transplantation
    • Peripheral Blood Progenitor Cell Transplantation
    • Peripheral Stem Cell Support
    • Peripheral Stem Cell Transplantation
  • Drug: Prednisone
    Given PO
    Other Names:
    • .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
  • Procedure: Syngeneic Bone Marrow Transplantation
    Undergo syngeneic bone marrow transplantation
Study Arms  ICMJE Experimental: Treatment (immunosuppressive therapy followed by transplant)
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 peripheral blood stem cell transplant on day 0. Patients also receive prednisone PO QD on days 7-21, followed by 2 week taper.
Interventions:
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 6, 2016)
40
Original Enrollment  ICMJE
 (submitted: July 15, 2008)
20
Estimated Study Completion Date  ICMJE December 1, 2021
Estimated Primary Completion Date March 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (only patients with relapsing/remitting multiple sclerosis [MS] will be included)
    • 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) < 60%, 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 < 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bernie McLaughlin 206.667-4916 bmclaugh@fredhutch.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00716066
Other Study ID Numbers  ICMJE 2260.00
NCI-2010-00403 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2260.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG9213030 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: George Georges Fred Hutch/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP