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

Myelogenous Leukemia, Acute Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01641250
• Other study ID #: BP28085
• Secondary ID: 2012-001027-12
• Status: Completed
• Phase: Phase 1
• First received: July 12, 2012
• Last updated: November 1, 2016
• Start date: August 2012
• Est. completion date: February 2015

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Francaise de Secrurite Sanitaire des Produits de Sante
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelogenous Leukemia, Acute

Intervention

Drug:
• RO5429083
Multiple escalating doses
• cytarabine
1000 mg/m2 iv daily for 5 consecutive days, up to 4 cycles

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

France,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence of adverse events (including maximum tolerated dose/optimal biological dose)		approximately 24 months	No
Secondary	Clinical response according to hematologic malignancy assessments		approximately 24 months	No
Secondary	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	No
Secondary	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	No
Secondary	Pharmacodynamics: Biomarker levels in blood/bone marrow		Pre-dose and up to 96 hrs post-dose	No