This open label, Phase I study of RO6839921 is a dose-escalation study with two arms. Prior to investigations in either arm, patients in a single cohort, Cohort 0, will receive non-escalating, intravenous (IV) doses of RO6839921 daily on Days 1-5 of a 28-day cycle. Interim PK and safety data from this cohort will be evaluated before initiating dose-escalation. In arm A, RO6839921 will be given to patients with advanced solid tumor malignancies. In Arm B, RO6839921 will be given to patients with relapsed/refractory acute myeloid leukemia (AML). The arms will escalate independently. Escalation will begin in solid tumor patients (Arm A) in single patient cohorts, using a new Continual Reassessment Method (n-CRM). Escalation for AML patients will be initiated at or below the dose level that causes \>/= Grade 2 hematologic side effects in Arm A. Escalation in AML patients will follow a rolling 6 design. In both arms, RO6839921 will be administered by IV infusion on Days 1-5 of 28-day cycles. There will be no intrapatient dose escalation. All patients may be treated until disease progression/relapse or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
68
Non-escalating IV doses given on Days 1-5 of Cycle 1.
Escalating IV doses of RO6839921 in solid tumor patients. Dose escalation will be calculated using the new Continual Reassessment Method (nCRM). RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation.
Escalating IV doses of RO6839921 in AML patients. Escalation will follow an adapted rolling 6 design. Starting dose \</= dose inducing Grade 2 toxicity in patients with solid tumors. RO6839921 will be given on Days 1-5 of 28-day cycles. Treatment will continue until disease progression, unacceptable toxicity or study discontinuation.
University of Colorado
Aurora, Colorado, United States
Washington University
St Louis, Missouri, United States
Medical University of South Carolina; Hollings Cancer Center
Charleston, South Carolina, United States
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
Toronto, Ontario, Canada
Jewish General Hospital / McGill University
Montreal, Quebec, Canada
Incidence of adverse events
Time frame: Approximately 1 year
Incidence of dose-limiting toxicities
Time frame: Approximately 1 year
Plasma area under the concentration-time curve (AUC) of RO6839921.
Time frame: Up to Day 22
Changes in serum macrophage inhibitory cytokine-1 (MIC-1) expression measured by enzyme-linked immunosorbent assay (ELISA)
Time frame: Up to Day 22
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