Safety and Activity of SNX-5422 Plus Ibrutinib in CLL
26. juli 2018 opdateret af: Esanex Inc.
A Phase 1, Open-label Study of SNX-5422 and Ibrutinib in Chronic Lymphocytic Leukemia Subjects With a Mutation in Bruton's Tyrosine Kinase
SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor of the molecular chaperone heat shock protein 90 (HSP90).
Hsp90 inhibitors may overcome ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the addition of SNX-5422 to an established dose of ibrutinib will result in the removal of mutated BTK from blood mononuclear cells and/or prevents or delays disease progression of subjects with CLL
Studieoversigt
Detaljeret beskrivelse
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not considered curable outside of allogeneic stem cell transplantation.
BTK is a critical kinase in the B cell receptor signaling pathway. This pathway is amplified in CLL and results in amplification of proliferation and anti-apoptotic signals. By inhibiting BTK, ibrutinib eliminates the activation of these pro-survival pathways and microenvironment survival signals. While response to ibrutinib has been high with therapy well-tolerated overall, some patients have relapsed while others have been taken off therapy for toxicity or other reasons. Relapse in CLL can be mediated by at least two separate mechanisms. One is by mutations in BTK, which both decrease ibrutinib's affinity for BTK, and also changes the binding from irreversible to reversible. This is a proof of concept study to investigate whether the addition of SNX-5422 to an established dose of ibrutinib will reduce mutated BTK from CLL cells and/or prevents or delays disease progression of subjects with CLL.
This is an open-label study of SNX-5422 combined with ibrutinib. In each 28 day cycle, SNX-5422 will be dosed in the morning once every other day for 21 days, followed by a 7-day drug-free period. Subjects will continue to receive daily oral ibrutinib at their established dose level in the afternoon every day for 28 days. cycle
Undersøgelsestype
Interventionel
Fase
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Ohio
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Columbus, Ohio, Forenede Stater, 43210
- Wexner Medical Center, Ohio State University
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Males or non-pregnant, non-breastfeeding females 18 years-of-age or older
- A diagnosis of CLL as defined by IWCLL 2008 criteria and currently on treatment with ibrutinib without evidence of disease progression.
- No more than 4 prior lines of anti leukemia therapy (not including ibrutinib)
- Presence of mutated BTK in ≥ 4% of peripheral blood or bone marrow CLL cells, or ≥1% and rising on two separate measurements obtained at least 28 days apart.
- Life expectancy of at least 9 months
- Karnofsky performance score 70
- Adequate baseline laboratory assessments
- Signed informed consent form
- Recovered from toxicities of previous anticancer therapy to CTCAE Grade ≤ 1 with the exception of alopecia
- Subjects with reproductive capability must agree to practice adequate contraception methods.
Exclusion Criteria:
- Subjects experiencing toxicity with ibrutinib
- Prior treatment with any Hsp90 inhibitor.
- Major surgery or significant traumatic injury within 4 weeks of starting study treatment.
- Conventional chemotherapy or radiation within 4 weeks.
- The need for treatment with medications with clinically-relevant metabolism by the cytochrome P450 (CYP) 3A4 isoenzyme within 3 hours before or after administration of SNX-5422
- Screening ECG QTc interval 470 msec for females, 450 msec for males.
- At increased risk for developing prolonged QT interval unless corrected to within normal limits prior to first dose of SNX-5422
- Patients with chronic diarrhea or with Grade 2 or greater diarrhea despite appropriate medical management.
- Gastrointestinal diseases or conditions that could affect drug absorption
- Gastrointestinal diseases that could alter the assessment of safety, including irritable bowel syndrome, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
- History of documented adrenal dysfunction not due to malignancy.
- History of chronic liver disease.
- Active hepatitis A or B.
- Current alcohol dependence or drug abuse.
- Use of an investigational treatment (except for ibrutinib) from 30 days prior to the first dose
- Glaucoma, retinitis pigmentosa, macular degeneration, or any retinal changes detected by ophthalmological examination that are considered clinically important by examiner.
- Psychological or social reasons that would hinder or prevent compliance with the requirements of the protocol or compromise the informed consent process.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
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 |
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Eksperimentel: SNX-5422 plus ibrutinib
Open-label administration of SNX-5422 capsules dosed in the morning once every other day for 21 days (11 doses) followed by a 7 day drug free period and daily with the established ibrutinib dose for 28 days of a 28-days cycle.
Subjects will repeat the 28-day schedule until the cancer progresses or the subject is unable to tolerate the therapy
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SNX-5422 kapsel(er) doseret hver anden dag i 21 dage ud af en 28-dages behandlingscyklus til en samlet dosis på 56 mg/m2 SNX-5422.
Forsøgspersoner vil selv administrere daglig oral ibrutinib om eftermiddagen med mindst 8 timers mellemrum fra SNX-5422 i 28 dage af hver cyklus.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Efficacy of the combination of SNX-5422 and ibrutinib
Tidsramme: Every 12 weeks up to 52 weeks
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Change in percent of mutated BTK in CLL cells
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Every 12 weeks up to 52 weeks
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Antal forsøgspersoner, der rapporterer uønskede hændelser
Tidsramme: Dag 28 i hver 4-ugers cyklus fra randomisering op til 52 uger
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Hyppighed og sværhedsgrad af uønskede hændelser
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Dag 28 i hver 4-ugers cyklus fra randomisering op til 52 uger
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Time to disease progression
Tidsramme: Up to 52 weeks
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Elapsed time for each subject from randomization to relapse of disease up to 52 weeks
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Up to 52 weeks
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Clinical Laboratory testing
Tidsramme: Day 28 of each 4 week cycle from randomization up to 52 weeks
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Absolute values and changes from baseline for each subject using standard clinical chemistry, hematology and urinalysis parameters
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Day 28 of each 4 week cycle from randomization up to 52 weeks
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Electrocardiogram
Tidsramme: Pre-dose on Day 1 of each 4 week cycle from randomization up to 52 weeks
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Digital 12-lead ECG using standard recording methods at trough drug levels.
All ECG recordings will be analyzed for PR, RR, QT intervals, and for morphology.
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Pre-dose on Day 1 of each 4 week cycle from randomization up to 52 weeks
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
2. februar 2017
Primær færdiggørelse (Faktiske)
1. juli 2018
Studieafslutning (Faktiske)
1. juli 2018
Datoer for studieregistrering
Først indsendt
20. september 2016
Først indsendt, der opfyldte QC-kriterier
22. september 2016
Først opslået (Skøn)
26. september 2016
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
30. juli 2018
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
26. juli 2018
Sidst verificeret
1. juli 2018
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Andre undersøgelses-id-numre
- SNX-5422-CLN1-011
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Ingen
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
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