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).

Hoffmann-La Roche0 sites44 target enrollmentAugust 2012

ConditionsMyelogenous Leukemia, Acute

Interventionscytarabine RO5429083

DrugsRO5429083 cytarabine

Overview

Phase: Phase 1
Intervention: cytarabine
Conditions: Myelogenous Leukemia, Acute
Sponsor: Hoffmann-La Roche
Enrollment: 44
Primary Endpoint: Safety: Incidence of adverse events (including maximum tolerated dose/optimal biological dose)
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 2012

End Date

February 2015

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Part B: RO5429083 + cytarabine

Intervention: cytarabine

Part A: RO5429083

Intervention: RO5429083

Part B: RO5429083 + cytarabine

Intervention: RO5429083

Outcomes

Primary Outcomes

Safety: Incidence of adverse events (including maximum tolerated dose/optimal biological dose)

Time Frame: approximately 24 months

Secondary Outcomes

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)