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A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome

11. november 2015 oppdatert av: Hoffmann-La Roche

A PHASE IB/II STUDY TO EVALUATE THE SAFETY AND EFFICACY OF VISMODEGIB IN RELAPSED/REFRACTORY ACUTE MYELOGENOUS LEUKEMIA (AML) AND RELAPSED/REFRACTORY HIGH-RISK MYELODYSPLASTIC SYNDROME (MDS)

This study will assess the safety and efficacy of vismodegib in patients with relapsed/refractory acute myelogenous leukemia (AML) and relapsed/refractory high-risk myelodysplastic syndrome (MDS). Patients in Cohort 1 will receive single-agent vismodegib 150 mg orally daily. In Cohort 2, patients will receive vismodegib 150 mg orally daily in combination with cytarabine 20 mg subcutaneously for 10 days.

Anticipated time on study treatment is until disease progression, intolerable toxicity, or patient withdrawal of consent.

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Faktiske)

38

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6L5X8
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
      • Montreal, Quebec, Canada, H3T 1E2
  • Forente stater
    • California
      • Stanford, California, Forente stater, 94305
    • Michigan
      • Ann Arbor, Michigan, Forente stater, 48109
    • Missouri
      • Kansas City, Missouri, Forente stater, 64131
    • New York
      • New York, New York, Forente stater, 10065
    • Texas
      • Houston, Texas, Forente stater, 77030
  • Tyskland
      • Braunschweig, Tyskland, 38114
      • Essen, Tyskland, 45122
      • Hamburg, Tyskland, 20246
      • Heidelberg, Tyskland, 69120
      • Münster, Tyskland, 48149

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Patients with documented relapsed or refractory AML, except acute promyelocytic leukemia (APL [M3 subtype]), or relapsed or refractory high-risk MDS (high-risk MDS defined as International Prognostic Scoring System (IPSS) Int-2 or high and >/= 10% blasts in bone marrow)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  • Negative serum pregnancy test for women of childbearing potential and use of two forms of contraception while enrolled in the study and for 7 months after the patient discontinues from study
  • Male patients with female partners of childbearing potential must agree to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 2 months after the last dose of vismodegib
  • All non-hematological adverse events of any prior chemotherapy, surgery, or radiotherapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade </= 2 prior to starting therapy
  • Adequate hepatic and renal function

Exclusion Criteria:

  • Prior treatment with a Hh pathway inhibitor
  • Prior therapy for the treatment of malignancy within 14 days of Day 1, with the exception of:

Hydroxyurea in patients who need to continue this agent to maintain white blood cell (WBC) counts </= 50,000/mL. Hydroxyurea must be discontinued by Day 14 of the study

  • Current evidence of active central nervous system (CNS) leukemia
  • Any other active malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix)
  • Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

Unstable angina, symptomatic or otherwise uncontrolled arrhythmia requiring medication (does not include stable, lone atrial fibrillation), or myocardial infarction </= 6 months before study treatment start Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study

  • Pregnant or breast-feeding women
  • Patients who refuse to potentially receive blood products and/or have a severe hypersensitivity to blood products

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Vismodegib
Legemiddel: cytarabine
Cohort 2: 20 mg sc daily for 10 days starting Day 1, with a possible further cycle of 20 mg sc daily for 5 days starting no earlier than Day 29
Legemiddel: vismodegib
Cohorts 1 and 2: 150 mg orally daily
Andre navn:
  • RO5450815

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8
Tidsramme: Week 8
CR was defined as achieved if the neutrophils count was greater than (>) 1000 cells per microliter (µL), platelets count >100000/µL, bone marrow blasts percentage (%) less than (<) 5, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of extra medullary disease (EMD). CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils >1000 cells/µL or Not applicable [NA] or platelets count >100000/µL or NA), bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods.
Week 8

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment
Tidsramme: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
CR was defined as achieved if the neutrophils count >1000 cells/µL, platelets count >100000/µL, bone marrow blasts <5%, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of EMD. CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils > 1000 cells/µL or NA or platelets count >100000/µL or NA, bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods. The 95% confidence intervals (CI) were constructed using Blyth-Still-Cassella method.
Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Duration of Overall Response (DOR)
Tidsramme: Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
DOR is defined as the time from the first occurrence of a documented overall response to the time of relapse, as determined by the investigator using International Working Group (IWG) criteria (Participants not falling under any of the response criteria [CR or CRi or MLFS or PR] described under outcome measure 1 were considered as non-responders) or death from any cause during the study (defined as death within 30 days after the last dose of study drug).
Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Median Overall Survival (OS) Time
Tidsramme: Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
OS was defined as the time from start of study drug to death from any cause. OS was estimated using Kaplan-Meier analysis. Participants alive at the last date known to be alive were censored for the analysis.
Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
Percentage of Participants With an Event of Death During the Study
Tidsramme: Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
Pharmacokinetics (PK): Steady-state Plasma Concentration of Vismodegib
Tidsramme: Predose on Days 8, 29 and 57
PK data was planned to be reported only if the results of Cohort 2 are available.
Predose on Days 8, 29 and 57
Area Under the Concentration-time Curve (AUC) of Cytarabine
Tidsramme: Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29
PK data was planned to be reported only if the results of Cohort 2 are available.
Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Hoffmann-La Roche

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. september 2013

Primær fullføring (Faktiske)

1. november 2014

Studiet fullført (Faktiske)

1. november 2014

Datoer for studieregistrering

Først innsendt

11. juni 2013

Først innsendt som oppfylte QC-kriteriene

14. juni 2013

Først lagt ut (Anslag)

19. juni 2013

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

15. desember 2015

Siste oppdatering sendt inn som oppfylte QC-kriteriene

11. november 2015

Sist bekreftet

1. november 2015

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • GO28852
  • 2013-001570-14 (EudraCT-nummer)

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