A Study of RO5045337 in Combination With Cytarabine in Patients With Acute Myelogenous Leukemia

Myelogenous Leukemia, Acute Clinical Trial

Official title:

A Multicenter, Open Label, Phase 1B Study of Escalating Doses of RO5045337 Administered Orally, With Cytarabine Administered A) Subcutaneously, or B) Intravenously, in Patients With Acute Myelogenous Leukemia (AML)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01635296
• Other study ID #: NP28023
• Secondary ID: 2011-006252-36
• Status: Completed
• Phase: Phase 1
• First received: June 12, 2012
• Last updated: November 1, 2016
• Start date: July 2012
• Est. completion date: October 2013

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This multi-center, open-label, Phase 1b study will evaluate the safety, pharmacokinetics and efficacy of RO5045337 in combination with cytarabine in patients with acute myelogenous leukemia. In Arm A, cohorts of previously untreated patients deemed unsuitable for standard induction therapy will receive escalating oral doses of RO5045377 and cytarabine 20 mg/m2 subcutaneously daily for Days 1 to 10 of each 28-day cycle. In Arm B, cohorts of patients who have relapsed or are refractory after at least one cytarabine/anthracycline containing regimen will receive escalating oral doses of RO5045377 on Days 1 to 5 and cytarabine 1 gm/m2 intravenously on Days 1 to 6 of each 28-day cycle. Patients will receive up to 4 cycles of therapy, patients in Arm A who achieve hematologic response may continue additional cycles until disease progression.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• Patients with histologically or cytologically documented acute myelogenous leukemia appropriate for cytarabine therapy including:

• Arm A: Patients who have not received prior standard induction chemotherapy, considered unsuitable for standard induction therapy

• Arm B: Patients who have failed their 1st or greater line of standard induction chemotherapy (primary refractory) or patients who originally achieved a complete response but are currently in first or greater relapse

• 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

• Adequate hepatic and renal function

• Patient must be willing to submit the blood sampling and bone marrow sampling for PK and PD analyses and exploratory biomarkers

Exclusion Criteria:

• History of allergic or toxic reactions attributed to cytarabine or a history of allergic reactions to components of the formulated product

• Current evidence of CNS leukemia

• Any severe and/or uncontrolled medical condition or other conditions that could affect the participation in the study

• Pregnant or breastfeeding women

• HIV-positive patients receiving combination anti-retroviral therapy

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy 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:
• RO5045377
Multiple escalating oral doses, Days 1 to 10 of each 28-day cycle
• RO5045377
Multiple escalating oral doses, Days 1 to 5 of each 28-day cycle
• cytarabine
20 mg/m2 sc, Days 1 to 10 of each 28-day cycle
• cytarabine
1 gm/m2 iv, Days 1 to 6 of each 28-day cycle

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose/dose-limiting toxicities		approximately 12 months	Yes
Primary	Safety: Incidence of adverse events		approximately 12 months	No
Secondary	Efficacy: Hematologic response		approximately 1 year	No
Secondary	Pharmacodynamics: Biomarkers (MIC-1, protein, nucleic acid, other) from bone marrow/buccal tissue/blood		Pre-dose (and up to 12 hours post-dose Day 1 and Day 10 or Day 5)	No
Secondary	Pharmacokinetics: Cmax/area under the concentration-time curve		Pre-dose and up to 12 hours post-dose Day 1 and Day 10 or Day 5	No