A Multi-Center, Open-Label, Phase 1/1b Study of Escalating Doses of RO5503781 Administered Orally as 1) a Single Agent, 2) In Combination With Cytarabine, or 3) With Cytarabine and Anthracycline and 4) Assessing PK and Safety of New Optimized Formulation of RO5503781 With Cytarabine in Patients With Acute Myelogenous Leukemia (AML)
Brief SummaryThis 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.
PhasePhase 1 - a new treatment that has not been tested, and researchers are looking for the best way to administer the treatment and how much can be given safely. Phase I trials are usually offered only to patients with advanced disease who would not be helped by other known treatments. Some patients are helped by these treatments, although in this early stage physicians don’t really know if the treatment will be effective.
Inclusion and Exclusion 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.
- 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.
- Unknown facility, San Antonio, Texas, 78229
- Unknown facility, Houston, Texas, 77030