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

Study Overview
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Brief Summary
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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.

Official Title
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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).

Conditions
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Myelogenous Leukemia, Acute

Intervention / Treatment
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* Drug: RO5429083
* Drug: cytarabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |