Autologous Peripheral Blood Stem Cell Transplant for Neurologic Autoimmune Diseases

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT00716066
• Collaborator: (none)
• Enrollment: 80
• Locations: 3
• Arm: 1
• Duration (Months): 300.9
• Patients Per Site: 26.7
• Patients Per Site Per Month: 0.1

Study Details

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 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.

Condition or Disease	Intervention/Treatment	Phase
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	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	Phase 2

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 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jun 1, 2008
• Anticipated Primary Completion Date: Jan 30, 2028
• Anticipated Study Completion Date: Jun 30, 2033

Arms and Interventions

Arm

Intervention/Treatment

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.

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 Names: 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 154-93-8 ; 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 147-94-4 ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 33419-42-0 ; 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 148-82-3 ; 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 53-03-2 ; Procedure: Syngeneic Bone Marrow Transplantation; Undergo syngeneic bone marrow transplantation

Outcome Measures

Primary Outcome Measures

1. Incidence of grades 4-5 regimen-related toxicity [Up to 1 year 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 365 days after transplant will be defined as regimen-related toxicity.

Secondary Outcome Measures

1. Transplant-related mortality [Within 100 days post-transplant]

   Defined as death within the first 100 days of transplant due to transplant-related complications.

2. Disease responses [Up to 5 years]

   Assessed by clinical, laboratory and radiologic evaluation

3. Engraftment kinetics [Over first 60 days post-transplant]

   Monitored for engraftment kinetics of granulocytes, platelets and red cells post-transplant.

4. 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)]

   Efficacy of peripheral blood stem cell mobilization as evaluated by total number of harvested CD34+cells/kg, for autologous transplant.

5. 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)]

   Subjects are evaluated by standardized clinical neurologic tests specific to autoimmune disease type.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 71 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
2	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
3	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307

Sponsors and Collaborators

• Fred Hutchinson Cancer Center

Investigators

• Principal Investigator: George Georges, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00716066
• Other Study ID Numbers: 2260.00; NCI-2010-00403; 2260.00; RG9213030
• First Posted: Jul 16, 2008
• Last Update Posted: Jun 23, 2022
• Last Verified: Jun 1, 2022

• Keywords provided by Fred Hutchinson Cancer Center: 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
• Additional relevant MeSH terms: Myasthenia Gravis; Lambert-Eaton Myasthenic Syndrome; Opsoclonus-Myoclonus Syndrome; Muscle Weakness; Multiple Sclerosis; Encephalitis; Polyneuropathies; Neuromyelitis Optica; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Myoclonus; Nervous System Diseases; Stiff-Person Syndrome; Ocular Motility Disorders; Autoimmune Diseases of the Nervous System; Vasculitis, Central Nervous System; Vasculitis; Autoimmune Diseases; Disease; Syndrome; Sclerosis; Cytarabine; Prednisone; Cortisone; Etoposide; Etoposide phosphate; Melphalan; Mechlorethamine; Carmustine; Podophyllotoxin; Nitrogen Mustard Compounds; Thymoglobulin; Antilymphocyte Serum

Study Results

No Results Posted as of Jun 23, 2022