Clinical trial NCT01641250: A Study of RO5429083 Alone or in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myelogenous Leukemia, Acute
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-07-16
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety: Incidence of adverse events (including maximum tolerated dose/optimal biological dose)
timeFrame: approximately 24 months
Secondary outcomes:
measure: Clinical response according to hematologic malignancy assessments
timeFrame: approximately 24 months
measure: Pharmacokinetics o RO5429083 alone and in combination with cytarabine: Area under the concentration-time curve (AUC)
timeFrame: Pre-dose and up to 96 hrs post-dose
measure: Pharmacokinetics of cytarabine in combination with RO5429083: Area under the concentration-time curve (AUC)
timeFrame: Pre-dose and up to 24 hrs post-dose, Cycles 1 and 3
measure: Pharmacodynamics: Biomarker levels in blood/bone marrow
timeFrame: Pre-dose and up to 96 hrs post-dose
Other outcomes:
Locations:
city: Marseille
country: France
city: Nantes
country: France
city: Paris
country: France
city: Toulouse
country: France
city: Aachen
country: Germany
city: Hamburg
country: Germany
city: Ulm
country: Germany
city: Bologna
country: Italy
state: Emilia-Romagna
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: