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

NCT01635296 | Completed Phase 1

• 2 other identifiers: NP280232011-006252-36
• Study Type: interventional
• Target: 43
• Locations: 5 countries
• Sites: 9

Brief 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.

Conditions

Myelogenous Leukemia, Acute

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose/dose-limiting toxicities

  approximately 12 months

• Safety: Incidence of adverse events

  approximately 12 months

Secondary Outcomes (3)

• Efficacy: Hematologic response

  approximately 1 year

• 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)

• 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

Study Arms (2)

A: Previously untreated

EXPERIMENTAL

Drug: RO5045377; Drug: cytarabine

B: Relapse/Refractory

EXPERIMENTAL

Drug: RO5045377; Drug: cytarabine

Interventions

RO5045377 DRUG

Multiple escalating oral doses, Days 1 to 10 of each 28-day cycle

A: Previously untreated

cytarabine DRUG

20 mg/m2 sc, Days 1 to 10 of each 28-day cycle

A: Previously untreated

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (9)

Unknown Facility

Valhalla, New York, 10595, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19107, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

Toronto, Ontario, M5G 2M9, Canada

Location

Unknown Facility

Montreal, Quebec, H3T 1E2, Canada

Location

Unknown Facility

Marseille, 13273, France

Location

Unknown Facility

Bologna, Emilia-Romagna, 40138, Italy

Location

Unknown Facility

Glasgow, G12 0YN, United Kingdom

Location

Unknown Facility

Manchester, M204BX, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2012
• First Posted: July 9, 2012
• Study Start: July 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

FR (1); CA (2); US (3); GB (2); IT (1)