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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00403 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2260.00 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| RG9213030 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (immunosuppressive therapy followed by transplant) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anti-Thymocyte Globulin | Biological | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 1 year post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Transplant-related mortality | Defined as death within the first 100 days of transplant due to transplant-related complications. | Within 100 days post-transplant |
| Disease responses | Assessed by clinical, laboratory and radiologic evaluation |
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Inclusion Criteria:
Patients with an autoimmune disorder of the central or peripheral nervous system will be eligible; this will include:
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:
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
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| Name | Affiliation | Role |
|---|---|---|
| Leona Holmberg | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Colorado Blood Cancer Institute | Denver | Colorado | 80218 | United States | ||
| Fred Hutch/University of Washington Cancer Consortium |
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| Autologous Hematopoietic Stem Cell Transplantation | Procedure | Undergo autologous or syngeneic stem cell transplantation |
|
|
| Carmustine | Drug | Given IV |
|
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| Cytarabine | Drug | Given IV |
|
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| Etoposide | Drug | Given IV |
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| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Melphalan | Drug | Given IV |
|
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| Peripheral Blood Stem Cell Transplantation | Procedure | Undergo autologous or syngeneic stem cell transplantation |
|
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| Prednisone | Drug | Given PO |
|
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| Syngeneic Bone Marrow Transplantation | Procedure | Undergo syngeneic bone marrow transplantation |
|
| Up to 5 years |
| Engraftment kinetics | Monitored for engraftment kinetics of granulocytes, platelets and red cells post-transplant. | 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 | Efficacy of peripheral blood stem cell mobilization as evaluated by total number of harvested CD34+cells/kg, for autologous transplant. | Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations) |
| 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. | Baseline to post mobilization, assessed up to 20 days after starting final mobilization (up to two mobilizations) |
| Seattle |
| Washington |
| 98109 |
| United States |
| Swedish Medical Center-First Hill | Seattle | Washington | 98122-4307 | United States |
| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| D020274 | Autoimmune Diseases of the Nervous System |
| D016750 | Stiff-Person Syndrome |
| D020293 | Vasculitis, Central Nervous System |
| D020277 | Polyradiculoneuropathy, Chronic Inflammatory Demyelinating |
| D015624 | Lambert-Eaton Myasthenic Syndrome |
| D009157 | Myasthenia Gravis |
| D009471 | Neuromyelitis Optica |
| D053578 | Opsoclonus-Myoclonus Syndrome |
| C535291 | Rasmussen subacute encephalitis |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D014657 | Vasculitis |
| D011129 | Polyradiculoneuropathy |
| D003711 | Demyelinating Diseases |
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020361 | Paraneoplastic Syndromes, Nervous System |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010257 | Paraneoplastic Syndromes |
| D019636 | Neurodegenerative Diseases |
| D020511 | Neuromuscular Junction Diseases |
| D009188 | Myelitis, Transverse |
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D009902 | Optic Neuritis |
| D009901 | Optic Nerve Diseases |
| D003389 | Cranial Nerve Diseases |
| D005128 | Eye Diseases |
| D015835 | Ocular Motility Disorders |
| D009207 | Myoclonus |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| D000961 | Antilymphocyte Serum |
| C512542 | thymoglobulin |
| D002330 | Carmustine |
| C574855 | carmustine, poliferprosan 20 drug combination |
| D003561 | Cytarabine |
| D005047 | Etoposide |
| D008558 | Melphalan |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D011241 | Prednisone |
| C407664 | deltacortene |
| C036266 | prednylidene |
| ID | Term |
|---|---|
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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