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

This study is currently recruiting participants.
Verified March 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00716066
First received: July 15, 2008
Last updated: March 17, 2014
Last verified: March 2014

July 15, 2008
March 17, 2014
June 2008
June 2014   (final data collection date for primary outcome measure)
Incidence of grades 4-5 regimen-related toxicity as assessed by the Regimen Related Toxicity Scale [ Time Frame: Within 28 days post-transplant ] [ Designated as safety issue: Yes ]
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.
  • Incidence of grades 4-5 regimen-related toxicity [ Designated as safety issue: Yes ]
  • Incidence of severe transplant-related complications [ Designated as safety issue: Yes ]
  • Transplant-related mortality [ Designated as safety issue: Yes ]
  • Early disease progression [ Designated as safety issue: No ]
  • Loss of neurological function [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00716066 on ClinicalTrials.gov Archive Site
  • Transplant-related mortality [ Time Frame: Within 100 days post-transplant ] [ Designated as safety issue: No ]
    Defined as death within the first 100 days of transplant due to transplant-related complications.
  • Disease responses as assessed by clinical, laboratory and radiologic evaluation [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Engraftment kinetics [ Time Frame: Over first 60 days post-transplant ] [ Designated as safety issue: No ]
    Monitored for engraftment kinetics of granulocytes, platelets and red cells post-transplant.
  • Efficacy of peripheral blood stem cell mobilization from syngeneic donors and autograft recipients [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Disease response as assessed by clinical, laboratory, and radiologic evaluation [ Designated as safety issue: No ]
  • Engraftment kinetics [ Designated as safety issue: No ]
  • Efficacy of peripheral blood stem cell mobilization from syngeneic donors and autograft recipients [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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
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

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Autoimmune Disorder
  • Biological: anti-thymocyte globulin
    Given IV
    Other Names:
    • ATG
    • ATGAM
    • lymphocyte immune globulin
    • Thymoglobulin
  • Drug: carmustine
    Given IV
    Other Names:
    • BCNU
    • BiCNU
    • bis-chloronitrosourea
  • Drug: cytarabine
    Given IV
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Drug: melphalan
    Given IV
    Other Names:
    • Alkeran
    • CB-3025
    • L-PAM
    • L-phenylalanine mustard
    • L-Sarcolysin
  • Drug: prednisone
    Given PO
    Other Names:
    • DeCortin
    • Deltra
  • Procedure: autologous hematopoietic stem cell transplantation
    Undergo autologous or syngeneic peripheral blood stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
    Undergo autologous or syngeneic peripheral blood stem cell transplantation
    Other Names:
    • PBPC transplantation
    • PBSC transplantation
    • peripheral blood progenitor cell transplantation
    • transplantation, peripheral blood stem cell
  • Procedure: syngeneic bone marrow transplantation
    Undergo syngeneic bone marrow transplantation
    Other Names:
    • bone marrow transplantation, syngeneic
    • transplantation, syngeneic bone marrow
  • Other: laboratory biomarker analysis
    Correlative studies
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
  • Drug: carmustine
  • Drug: cytarabine
  • Drug: etoposide
  • Drug: melphalan
  • Drug: prednisone
  • Procedure: autologous hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Procedure: syngeneic bone marrow transplantation
  • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
Not Provided
June 2014   (final data collection date for primary outcome measure)

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
Both
up to 70 Years
No
Not Provided
United States
 
NCT00716066
2260.00, NCI-2010-00403, 2260.00, P30CA015704
No
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: George Georges Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
March 2014

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