A Study of the Safety and Pharmacokinetics of RO6839921, An MDM2 Antagonist, in Patients With Advanced Cancers, Including Acute Myeloid Leukemia.
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|ClinicalTrials.gov Identifier: NCT02098967|
Recruitment Status : Active, not recruiting
First Posted : March 28, 2014
Last Update Posted : January 12, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Neoplasms, Myelogenous Leukemia, Acute||Drug: RO6839921||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||68 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multi-Center, Open-Label, First-in-Human, Phase I Dose-Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO6839921, An MDM2 Antagonist, Following Intravenous Administration in Patients With Advanced Malignancies, Including Acute Myeloid Leukemia (AML)|
|Actual Study Start Date :||April 21, 2014|
|Estimated Primary Completion Date :||May 16, 2018|
|Estimated Study Completion Date :||May 16, 2018|
|Experimental: Acute myeloid leukemia patients||
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.
|Experimental: Cohort 0||
Non-escalating IV doses given on Days 1-5 of Cycle 1.
|Experimental: Solid tumor patients||
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.
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02098967
|United States, Colorado|
|University of Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Missouri|
|Saint Louis, Missouri, United States, 63110|
|United States, South Carolina|
|Medical University of South Carolina; Hollings Cancer Center|
|Charleston, South Carolina, United States, 29425|
|University Health Network; Princess Margaret Hospital; Medical Oncology Dept|
|Toronto, Ontario, Canada, M5G 2M9|
|Jewish General Hospital / McGill University|
|Montreal, Quebec, Canada, H3T 1E2|
|Study Director:||Clinical Trials||Hoffmann-La Roche|