A Study of RO5429083 Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia

Open Label, Multicenter, Dose Escalation Phase 1a/b Study of RO5429083, Administered as Intravenous Infusion Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia (AML).

This multi-center, open-label study will evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of RO5429083 alone and in combination with cytarabine in patients with acute myelogenous leukemia. In Part A, patients will receive multiple escalating doses of RO5429083 intravenously. In Part B, patients will receive RO5429083 plus up to 4 cycles of cytarabine (1000 mg/m2 iv daily for 5 consecutive days). Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Study Overview

• Status: Completed
• Conditions: Myelogenous Leukemia, Acute
• Intervention / Treatment: Drug: RO5429083; Drug: cytarabine

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Marseille, France, 13273
  • Nantes, France, 44093
  • Paris, France, 75475
  • Toulouse, France, 31059
• Germany
  • Aachen, Germany, 52074
  • Hamburg, Germany, 20246
  • Ulm, Germany, 89081
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically or cytologically confirmed, acute myelogenous leukemia (all subtypes except acute promyelotic leukemia) according to WHO criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• All non-hematological adverse events of any prior chemotherapy, surgery, or radiotherapy must have resolved to NCI-CTC AE Grade < 2, except alopecia
• Adequate hepatic and renal function
• Patient must be willing to submit blood and bone marrow samples for PK and PD analyses and exploratory biomarkers

Exclusion Criteria:

• Patients 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
• History of allergic reactions attributed to components of cytarabine and/or the formulated product
• Current evidence of CNS leukemia
• Increased QTc interval (QTc > 470 ms), baseline resting bradycardia < 45 beats per minute, or baseline resting tachycardia < 100 beats per minute
• Family history of long QT syndrome or other risk factors for torsades de pointes, and/or the use of concomitant medications that prolong QT/QTc interval
• Uncontrollable intercurrent illness
• Pregnant or breast-feeding women

• HIV-positive patients receiving anti-retroviral therapy

  • Patients who refuse to potentially receive blood products and/or have a hypersensitivity to blood products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: RO5429083	Drug: RO5429083; Multiple escalating doses
Experimental: Part B: RO5429083 + cytarabine	Drug: RO5429083; Multiple escalating doses; Drug: cytarabine; 1000 mg/m2 iv daily for 5 consecutive days, up to 4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Incidence of adverse events (including maximum tolerated dose/optimal biological dose)	approximately 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical response according to hematologic malignancy assessments	approximately 24 months
Pharmacokinetics o RO5429083 alone and in combination with cytarabine: Area under the concentration-time curve (AUC)	Pre-dose and up to 96 hrs post-dose
Pharmacokinetics of cytarabine in combination with RO5429083: Area under the concentration-time curve (AUC)	Pre-dose and up to 24 hrs post-dose, Cycles 1 and 3
Pharmacodynamics: Biomarker levels in blood/bone marrow	Pre-dose and up to 96 hrs post-dose

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 16, 2012

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine
• Other Study ID Numbers: BP28085; 2012-001027-12 (EudraCT Number)