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

Phase 1

Completed

• Conditions: Myelogenous Leukemia, Acute
• Interventions: Drug: RO5429083; Drug: cytarabine

• Registration Number: NCT01641250
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-07-12
• Study First Submitted QC: 2012-07-12
• Study First Posted: 2012-07-16
• Study Start: 2012-08
• Primary Completion: 2015-02
• Study Completion: 2015-02
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-01
• Last Update Posted: 2016-11-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: RO5429083	RO5429083	-
Part B: RO5429083 + cytarabine	RO5429083	-
Part B: RO5429083 + cytarabine	cytarabine	-

Primary Outcome Measures

Name	Time	Method
Safety: Incidence of adverse events (including maximum tolerated dose/optimal biological dose)	approximately 24 months

Secondary Outcome Measures

Name	Time	Method
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
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