Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases

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

Running, not recruitingPhase 2MS (type not specified)NCT00716066

What it found

Still running

No result yet.

What was tested

Treatment tested

  • Antilymphocyte immunoglobulin (horse)
  • Autologous Hematopoietic Stem Cell Transplantation
  • Carmustine

    DNA inhibitor|Glutathione reductase inhibitor|RNA inhibitor

  • Cytarabine

    DNA inhibitor|DNA polymerase (alpha/delta/epsilon) inhibitor|RNA inhibitor

  • Etoposide

    DNA topoisomerase II inhibitor

  • Laboratory Biomarker Analysis
  • Melphalan

    DNA inhibitor

  • Peripheral Blood Stem Cell Transplantation
  • Prednisone

    Glucocorticoid receptor agonist

  • Syngeneic Bone Marrow Transplantation

What it measured

Main measures

  • Incidence of grades 4-5 regimen-related toxicity

    Up to 1 year post-transplant

    Safety

Other measures (5)

  • Transplant-related mortality

    Within 100 days post-transplant

  • Disease responses

    Up to 5 years

  • Engraftment kinetics

    Over first 60 days 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

    Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations)

    Immune response

  • Number of subjects with an exacerbation of autoimmune disease symptoms secondary to G-CSF (filgrastim) during peripheral blood stem cell mobilization

    Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations)

    Blood or spinal fluid markers

Who could take part

MS (type not specified) · Up to 71

Show the full 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

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

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.

Papers

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    History

      1. Started

        Jun 2008

      2. Main results due

        Dec 2025

      3. Finished

        Jan 2030

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