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A Study of RO5503781 as a Single Agent or in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia

24 janvier 2017 mis à jour par: Hoffmann-La Roche

A Multi-Center, Open-Label, Phase 1/1b Study of Escalating Doses of RO5503781 Administered Orally as 1) a Single Agent, 2) In Combination With Cytarabine, or 3) With Cytarabine and Anthracycline and 4) Assessing PK and Safety of New Optimized Formulation of RO5503781 With Cytarabine in Patients With Acute Myelogenous Leukemia (AML)

This Phase 1/1b, open-label study will evaluate the safety and pharmacokinetics of escalating doses of RO5503781 as a single agent or in combination with cytarabine in participants with acute myelogenous leukemia. In Part 1, RO5503781 will be administered in escalating doses as a single agent, and in Part 2, RO5503781 will be administered in combination with cytarabine. An optional Part 3 in which RO5503781 will be administered with cytarabine and anthracycline may be considered . In Part 4, the safety and pharmacokinetic profile of an optimized formulation of RO5503781 in combination with cytarabine will be assessed.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

122

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Australie
    • Victoria
      • Melbourne, Victoria, Australie, 3000
        • Peter MacCallum Cancer Centre
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
  • Corée, République de
      • Seoul, Corée, République de, 03080
        • Seoul National Uni Hospital; Dept. of Internal Medicine/Hematology/Oncology
      • Seoul, Corée, République de, 05505
        • Asan Medical Center
  • France
      • Marseille, France, 13273
        • Institut J Paoli I Calmettes; Onco Hematologie 2
  • Italie
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italie, 40138
        • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpigh
  • Royaume-Uni
      • Glasgow, Royaume-Uni, G12 0YN
        • The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit
  • États-Unis
    • California
      • Los Angeles, California, États-Unis, 90033
        • USC Norris Cancer Center
    • New York
      • Valhalla, New York, États-Unis, 10595
        • New York Medical College
    • Pennsylvania
      • Philadelphia, Pennsylvania, États-Unis, 19107
        • Thomas Jefferson University
    • Texas
      • San Antonio, Texas, États-Unis, 78229
        • Cancer Therapy & Research Ctr; Dept Institute for Drug Development

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  • Documented/confirmed acute myelogenous leukemia (AML), except for acute promyelocytic leukemia
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 in Part 1 and Part 2, participants enrolled in the extension/tail portion, Part 3 and Part 4 must have an ECOG performance status of 0 or 1
  • 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 less than or equal to (</=) 2 prior to starting therapy
  • Adequate hepatic and renal function
  • Willing to submit the blood sampling and bone marrow sampling required by protocol

Additional inclusion criteria for Parts 1-4 may apply.

Exclusion Criteria:

  • Participants receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 14 days of first receipt of study drug, with the exception of hydroxyurea as defined in protocol
  • History of allergic or toxic reactions attributed to cytarabine (Part 2) or history of allergic reactions to components of the formulated product
  • Current evidence of central nervous system (CNS) leukemia
  • Participants with severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • Participants with evidence of electrolyte imbalance greater than or equal to (>/=) Grade 2 which cannot be corrected prior to study initiation
  • Pregnant or breastfeeding women
  • Human immunodeficiency virus (HIV) - positive participants receiving anti-retroviral therapy
  • Participants who refuse to potentially receive blood products and/or have a hypersensitivity to blood products

Additional exclusion criteria for Parts 1-4 may apply.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Part 1: RO5503781
Participants will receive RO5503781 alone in escalating doses on Days 1 to 5 of each 28-day cycle until disease progression or unacceptable toxicity.
Médicament: RO5503781 MBP
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
Expérimental: Part 2: RO5503781 + Cytarabine
Participants will receive RO5503781 in escalating doses on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.
Médicament: RO5503781 MBP
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
Médicament: Cytarabine
Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m^2 IV infusion daily.
Expérimental: Part3:RO5503781+Cytarabine+Anthracycline
Participants will receive RO5503781 on Days 1 to 5, cytarabine on Days 1 to 7, and anthracycline (daunorubicin or idarubicin) on Days 1 to 3 of each 28-day cycle until disease progression or unacceptable toxicity.
Médicament: RO5503781 MBP
Participants will receive RO5503781 tablets daily (current formulation) containing microprecipitated bulk powder (MBP) at a starting dose of 400 milligrams (mg).
Médicament: Cytarabine
Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m^2 IV infusion daily.
Médicament: Idarubicin
Idarubicin will be administered as per standard clinical practice.
Médicament: Daunorubicin
Daunorubicin will be administered as per standard clinical practice.
Expérimental: Part 4: Optimized RO5503781 + Cytarabine
Participants will receive optimized RO5503781 formulation on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.
Médicament: Cytarabine
Parts 2 and 4: Participants will receive cytarabine 1000 milligrams per meter squared (mg/m^2) intravenous (IV) infusion daily. Part 3: Participants will receive cytarabine 100-200 mg/m^2 IV infusion daily.
Médicament: RO5503781 SDP
Participants will receive RO5503781 tablets daily (new optimized formulation) containing spray-dried powder (SDP) at recommended dose(s) for development from Phase 1b to Phase 3.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Maximum Tolerated Dose (MTD) and/ or Recommended Phase 2 Dose (RP2D) of RO5503781
Délai: Day 1 up to Day 42
Day 1 up to Day 42
Proportion of Participants with Dose-Limiting Toxicities (DLTs)
Délai: Day 1 up to Day 42
Day 1 up to Day 42
Safety: Proportion of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Délai: Baseline up to approximately 2 years
Baseline up to approximately 2 years

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) (in Micrograms per Milliliters [mcg/mL]) of RO5503781, Cytarabine,1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cycle (Cy) 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cycle (Cy) 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Time to Reach Maximum Plasma Concentrations (Tmax) in hours of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description).
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description).
Pharmacokinetics: Terminal Half-Life (t1/2) (in hours) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Area Under Plasma Concentration-Time Curve Over One Dosing Internal (AUCtau) (in mcg*hour/mL) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Area Under Plasma Concentration-Time Curve From 0 to the Last Measurable Concentration (AUClast) (in mcg*hour/mL) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Area Under Plasma Concentration-Time Curve From 0 to Infinity (AUCinf) (in mcg*hour/mL) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Apparent Oral Clearance (CL/F) (in liters/hour) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Apparent Volume of Distribution (V/F) (in liters) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacokinetics: Apparent Elimination Rate Constant (kel) (in 1/hour) of RO5503781, Cytarabine, 1-beta-D-Arabinofuranosyluracil, Daunorubicin, Daunorubicinol, Idarubicin, and Idarubicinol
Délai: Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Timeframe for RO5503781: Predose (0 hour [Hr]), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy 1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days) Timeframe for cytarabine, 1-beta-D-arabinofuranosyluracil (cytarabine metabolite): Parts 2,4: Predose (0Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Days 1, 5; Predose (0Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15; Part 3: Predose (0 Hr) on Cy1 Day 1; Predose (0 Hr), 1, 2, 3, 4, 6, 10 Hr Postdose on Cy1 Day 5; Cy1 Day 6 (Cy=28days) Timeframe for daunorubicin, daunorubicinol (daunorubicin metabolite), idarubicin, and idarubicinol (idarubicin metabolite): Part 3: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr Postdose on Cy 1 Days 1, 5; Predose (0 Hr) on Cy1 Day 2; Cy1 Day 6 (Cy length=28 days)
Predose (0 Hr) on Cy 1 Day 1 up to Cy 1 Day 15 (Cy length=28 days) (detailed timeframe for individual drug is provided in outcome measure description)
Pharmacodynamics: Macrophage Inhibitory Cytokine-1 (MIC1) Serum Levels
Délai: Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days)
Predose (0 Hr), and 1, 2, 3, 4, 6, 10 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy1 Day 2; Cy1 Day 6; Cy 1 Days 8, 9, 15 (Parts 1, 2, 4 only) (Cy length=28 days)
Pharmacodynamics: Proportion of Participants With Tumor Suppressor Protein 53 (p53) Mutation, as Assessed by Gene Sequencing and/or Research-Use AmpliChip p53 Test
Délai: Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Pharmacodynamics: Murine Double Minute-2 (MDM2) Messenger Ribonucleic Acid (mRNA) Expression, as Assessed by Quantitative Real Time Polymerase Chain Reaction (RT-PCR)
Délai: Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Predose (0 Hr), and 6 Hr postdose on Cy 1 Days 1, 5; predose (0 Hr) on Cy 1 Day 2; Cy 1 Day 6; at disease progression/relapse (up to approximately 3.25 years)
Proportion of Participants With Complete Remission (CR) as best response during study and follow up period, as Assessed Using Bone Marrow and Hematological Examinations
Délai: Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CR from occurrence of CR to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CR from occurrence of CR to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Complete Remission Without Platelet Recovery (CRp) as best response during study and follow up period as Assessed Using Bone Marrow and Hematological Examinations
Délai: Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRp from occurrence of CRp to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRp from occurrence of CRp to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Complete Remission With Insufficient Recovery of Peripheral Counts (CRi) or Morphologic Leukemia Free State (MLFS) as Best Response During Study and Follow Up as Assessed Using Bone Marrow and Hematological Examinations
Délai: Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRi from occurrence of CRi to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with CRi from occurrence of CRi to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Partial Response (PR) as Best Response During Study and Follow Up Period, as Assessed Using Bone Marrow and Hematological Examinations
Délai: Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with PR from occurrence of PR to 1 year (overall up to approximately 3.25 years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2 months for participants with PR from occurrence of PR to 1 year (overall up to approximately 3.25 years)
Proportion of Participants With Hematologic Improvement (SD/HI) as Best Response During Study and Follow Up Period, as Assessed Using Bone Marrow and Hematological Examinations
Délai: Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2months for participants with SD/HI from occurrence of SD/HI to 1 year (overall up to approximately 3.25years)
Day 1 of each treatment cycle starting from Cy 2 up to 28 days after last dose of RO5503781 (approximately 3.25 years); additionally, every 2months for participants with SD/HI from occurrence of SD/HI to 1 year (overall up to approximately 3.25years)
Proportion of Participants With Disease Progression as Best Response During Study and Follow Up Period
Délai: Baseline up to approximately 3.25 years
Baseline up to approximately 3.25 years

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Hoffmann-La Roche

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 février 2013

Achèvement primaire (Réel)

1 juin 2016

Achèvement de l'étude (Réel)

1 juin 2016

Dates d'inscription aux études

Première soumission

18 janvier 2013

Première soumission répondant aux critères de contrôle qualité

18 janvier 2013

Première publication (Estimation)

23 janvier 2013

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

25 janvier 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

24 janvier 2017

Dernière vérification

1 janvier 2017

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • NP28679
  • 2012-004882-41 (Numéro EudraCT)

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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