A Study of RO5503781 as a Single Agent or in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia

Roche

Status and phase: Completed; Phase 1

Conditions: Myelogenous Leukemia, Acute

Treatments: Drug: Daunorubicin; Drug: Idarubicin; Drug: RO5503781 SDP; Drug: Cytarabine; Drug: RO5503781 MBP

Study type: Interventional

Funder types: Industry

Identifiers

NCT01773408

2012-004882-41 (EudraCT Number)

NP28679

Details and patient eligibility

About

This Phase 1/1b, open-label study will evaluate the safety and pharmacokinetics of escalating doses of RO5503781 as a single agent or in combination with cytarabine in participants with acute myelogenous leukemia. In Part 1, RO5503781 will be administered in escalating doses as a single agent, and in Part 2, RO5503781 will be administered in combination with cytarabine. An optional Part 3 in which RO5503781 will be administered with cytarabine and anthracycline may be considered . In Part 4, the safety and pharmacokinetic profile of an optimized formulation of RO5503781 in combination with cytarabine will be assessed.

Enrollment: 122 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented/confirmed acute myelogenous leukemia (AML), except for acute promyelocytic leukemia
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 in Part 1 and Part 2, participants enrolled in the extension/tail portion, Part 3 and Part 4 must have an ECOG performance status of 0 or 1
• All non-hematological adverse events of any prior chemotherapy, surgery or radiotherapy must have resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade less than or equal to (</=) 2 prior to starting therapy
• Adequate hepatic and renal function
• Willing to submit the blood sampling and bone marrow sampling required by protocol

Additional inclusion criteria for Parts 1-4 may apply.

Exclusion criteria

• Participants 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 as defined in protocol
• History of allergic or toxic reactions attributed to cytarabine (Part 2) or history of allergic reactions to components of the formulated product
• Current evidence of central nervous system (CNS) leukemia
• Participants with severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Participants with evidence of electrolyte imbalance greater than or equal to (>/=) Grade 2 which cannot be corrected prior to study initiation
• Pregnant or breastfeeding women
• Human immunodeficiency virus (HIV) - positive participants receiving anti-retroviral therapy
• Participants who refuse to potentially receive blood products and/or have a hypersensitivity to blood products

Additional exclusion criteria for Parts 1-4 may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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122 participants in 4 patient groups

Part 1: RO5503781

Experimental group

Description:

Participants will receive RO5503781 alone in escalating doses on Days 1 to 5 of each 28-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: RO5503781 MBP

Part 2: RO5503781 + Cytarabine

Experimental group

Description:

Participants will receive RO5503781 in escalating doses on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: RO5503781 MBP

Drug: Cytarabine

Part3:RO5503781+Cytarabine+Anthracycline

Experimental group

Description:

Participants will receive RO5503781 on Days 1 to 5, cytarabine on Days 1 to 7, and anthracycline (daunorubicin or idarubicin) on Days 1 to 3 of each 28-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: RO5503781 MBP

Drug: Cytarabine

Drug: Idarubicin

Drug: Daunorubicin

Part 4: Optimized RO5503781 + Cytarabine

Experimental group

Description:

Participants will receive optimized RO5503781 formulation on Days 1 to 5 and cytarabine on Days 1 to 6 of each 28-day cycle until disease progression or unacceptable toxicity.

Treatment:

Drug: Cytarabine

Drug: RO5503781 SDP