- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT01307332
Advanced MRI Measures of Repair in Alemtuzumab Treated Patients (iCAMMS-IST)
Advanced Magnetic Resonance Imaging Measures of Repair in Alemtuzumab Treated Patients
There are two parts to this investigator sponsored trial (IST):
- To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
- To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). There are many forms of MS; although the majority are Relapsing Remitting (RRMS) representing approximately 80% of the cases. The disease appears to be more inflammatory in RRMS as manifested by an increase in Gadolinium (Gd) enhancement on MRI and an increase in inflammatory bio-assay markers.
Alemtuzumab; a humanized monoclonal antibody that targets the CD52 molecule present on T and B lymphocytes, natural killer (NK) cells, and monocytes and macrophages; effects rapid and sustained lymphocyte depletion and is approved for the treatment of B-cell chronic lymphocytic leukemia in many countries under the names CAMPATH or MabCAMPATH.
There are two parts to this Investigator Sponsored Trial (IST):
- To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
- To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V6T 2B5
- University of British Columbia Hospital
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
- Signed, informed consent form
- Age 18 to 50 years old (inclusive)
- Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 10 years of screening
- Onset of MS symptoms within 15 years of screening
- Neurostatus (EDSS) score 0.0 to 5.0 (inclusive)
- 2 MS attacks (first episode or relapse) occurring in the 24 months prior to screening, with 1 attack in the 12 months prior to screening, with objective neurological signs confirmed by a physician.
Exclusion Criteria:
- Received prior therapy for MS other than corticosteroids within 28 days of screening; e.g., interferon's, IV immunoglobulin, and glatiramer acetate
- Exposure to natalizumab within 6 months of screening
- Any prior exposure to mitoxantrone, mycophenolate mofetil, azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, rituximab, or any other immunosuppressive agent other than systemic corticosteroid treatment
- Has any progressive form of MS
- History of malignancy (exception for basal cell skin carcinoma)
- Previous hypersensitivity reaction to other immunoglobulin product
- Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
- CD4+, CD8+, or CD19+ (i.e., absolute CD3+CD4+, CD3+CD8+, or CD19+/mm3) count <LLN at Screening; if abnormal cell count(s) return to within normal limits, eligibility may be reassessed
- Seropositivity for human immunodeficiency virus (HIV)
- Significant autoimmune disease (e.g, immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel disease; severe psoriasis)
- Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies
- Active infection
- Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis.
- Infection with hepatitis B virus or hepatitis C virus
- Of childbearing potential with a positive serum pregnancy test
- Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period
- Major psychiatric disorder that is not adequately controlled by treatment
- Epileptic seizures that are not adequately controlled by treatment
- Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results
- Medical, psychiatric, cognitive, or other conditions
- Confirmed platelet count the lower limit of normal (LLN) of the evaluating laboratory at Screening or documented at 100,000/L within the past year on a sample without clumping
- Prior history of invasive fungal infections
- Cervical high risk human papilloma virus (HPV) positivity or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS).
- Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II (HTLV-I/II) (testing required in endemic regions only)
- Any other illness or infection (latent or active) that, in the Investigator's opinion, could be exacerbated by alemtuzumab treatment
- Any hepatic or renal function value grade 2 or higher at Screening, with the exception of hyperbilirubinemia due to Gilbert's syndrome.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: MabCampath-1h
Single arm, single cohort study, all subjects will be dosed with alemtuzumab.
|
Drug:10 mg/mL alemtuzumab intravenous infusion.
Form: Sterile, clear, colorless solution.
Dosage: 2 cycles.
Month 0 dosed over 5 consecutive days; month 12 dosed over 3 consecutive days.
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Changes in normal appearing white matter from baseline through month 24.
Tidsramme: 24 months
|
The MRI study is designed to identify possible mechanisms by which alemtuzumab acts to protect the brain from inflammation and how it may enhance repair through remyelination.
|
24 months
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
To identify specific changes in T cell subsets and functions in Relapsing Remitting Multiple Sclerosis from baseline through month 48.
Tidsramme: 48 months
|
Analyzing changes is immune responsiveness may reveal critical information about the mechanisms by which alemtuzumab acts, confirm the importance of specific immune cell types or molecules as targets for alemtuzumab treatment or may also be useful for monitoring drug effectiveness and safety.
|
48 months
|
Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Anthony Traboulsee, MD, University of British Columbia
Publikationer og nyttige links
Generelle publikationer
- Gilmore W, Lund BT, Li P, Levy AM, Kelland EE, Akbari O, Groshen S, Cen SY, Pelletier D, Weiner LP, Javed A, Dunn JE, Traboulsee AL. Repopulation of T, B, and NK cells following alemtuzumab treatment in relapsing-remitting multiple sclerosis. J Neuroinflammation. 2020 Jun 15;17(1):189. doi: 10.1186/s12974-020-01847-9.
- Coles AJ, Cox A, Le Page E, Jones J, Trip SA, Deans J, Seaman S, Miller DH, Hale G, Waldmann H, Compston DA. The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy. J Neurol. 2006 Jan;253(1):98-108. doi: 10.1007/s00415-005-0934-5. Epub 2005 Jul 27.
- CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- Multipel sclerose
- Sygdomme i immunsystemet
- RRMS
- FRK
- Sygdomme i nervesystemet
- Autoimmune sygdomme
- Alemtuzumab
- T-celler
- Recidiverende remitterende multipel sklerose
- Demyelinisering
- Demyeliniserende sygdomme
- Remyelinisering
- Autoimmune sygdomme i nervesystemet
- Demyeliniserende autoimmune sygdomme, CNS
- Tolerogenic
Yderligere relevante MeSH-vilkår
- Patologiske processer
- Sygdomme i nervesystemet
- Sygdomme i immunsystemet
- Demyeliniserende autoimmune sygdomme, CNS
- Autoimmune sygdomme i nervesystemet
- Demyeliniserende sygdomme
- Autoimmune sygdomme
- Multipel sclerose
- Sclerose
- Multipel sklerose, recidiverende-remitterende
- Antineoplastiske midler
- Antineoplastiske midler, immunologiske
- Alemtuzumab
Andre undersøgelses-id-numre
- H10-02482
- 142402 (Anden identifikator: Health Canada - NOL)
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .
Kliniske forsøg med Recidiverende remitterende multipel sklerose
-
BiocadRekrutteringRelapsing-remitting multipel sklerose (RRMS)Rusland
-
Centre Hospitalier Universitaire de NīmesRekrutteringMultipel sklerose (MS) - Relapsing-remittingFrankrig
-
Sichuan Academy of Medical SciencesBeijing Tiantan Hospital; Shandong Provincial Hospital; Tang-Du Hospital; First... og andre samarbejdspartnereIkke rekrutterer endnuMultipel sklerose (MS) Relapsing Remitting
-
Medipol UniversityRekrutteringMultipel sklerose (MS) - Relapsing-remittingTyrkiet (Türkiye)
-
Yeditepe UniversityThe Scientific and Technological Research Council of TurkeyAfsluttetMultipel sclerose | Multipel sklerose (MS) - Relapsing-remittingTyrkiet (Türkiye)
-
Northwestern UniversityTG Therapeutics, Inc.RekrutteringMultipel sclerose | Multipel sklerose (MS) - Relapsing-remittingForenede Stater
-
Cabaletta BioIkke rekrutterer endnuProgressiv multipel sklerose | Multipel sclerose | Multipel sklerose (tilbagefaldende overførelse) | Relapserende multipel sklerose (RMS) | Progressiv multipel sklerose (PMS) | Multipel sklerose (MS) - Relapsing-remitting | Multipel sklerose - Relapsing Remitting
-
University of AarhusRekrutteringMultipel sklerose (MS) - Relapsing-remittingDanmark
-
German University in CairoAfsluttetMultipel sklerose (MS) - Relapsing-remittingEgypten
-
National Institute of Allergy and Infectious Diseases...Autoimmunity Centers of ExcellenceAfsluttetMultipel sklerose (MS) - Relapsing-remittingForenede Stater
Kliniske forsøg med MabCampath-1h
-
Northwestern UniversityGenzyme, a Sanofi Company; Millennium Pharmaceuticals, Inc.Afsluttet
-
Genzyme, a Sanofi CompanyAfsluttetLeukæmi, lymfatisk, kronisk, B-celleJapan
-
M.D. Anderson Cancer CenterAfsluttetTilbagevendende T-celle prolymfocytisk leukæmi | T-celle prolymfocytisk leukæmiForenede Stater
-
Central Texas Neurology ConsultantsGenzyme, a Sanofi CompanyUkendt
-
CABYCGrupo Español de Linfomas y Transplante Autólogo de Médula ÓseaAfsluttetPode versus værtssygdomSpanien
-
University of GöttingenAfsluttetPerifert T-celle lymfom
-
University of Illinois at ChicagoAktiv, ikke rekrutterendeSeglcellesygdomForenede Stater
-
Genzyme, a Sanofi CompanyBayer Healthcare Pharmaceuticals, Inc./Bayer Schering PharmaAfsluttetB-celle kronisk lymfatisk leukæmi (B-CLL)Det Forenede Kongerige, Belgien, Frankrig, Forenede Stater, Tjekkiet, Serbien
-
Assistance Publique - Hôpitaux de ParisSociety for EndocrinologyRekrutteringParagangliom af hoved og halsFrankrig
-
Steven E. CoutreBayerAfsluttetLeukæmi | Kronisk lymfatisk leukæmi (CLL) | Kronisk leukæmi | B-celle leukæmiForenede Stater