A Study of Brequinar in Subjects With Relapsed/Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03760666|
Recruitment Status : Recruiting
First Posted : November 30, 2018
Last Update Posted : June 19, 2020
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Brequinar Drug: Brequinar + Ribavirin||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Subjects start dosing with brequinar alone; Cohort 2 subjects may roll over into ribavirin dosing; Cohort 3 subjects will start with brequinar alone then add ribavirin dosing.|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b/2a Open-label, Multi-center Study to Assess the Safety, Efficacy and Pharmacokinetics of Intrapatient Dose-adjusted Brequinar and Inhibition of Dihydroorotate Dehydrogenase (DHODH) in Adult Subjects With AML|
|Actual Study Start Date :||November 26, 2018|
|Estimated Primary Completion Date :||December 31, 2020|
|Estimated Study Completion Date :||June 30, 2021|
Brequinar dosed orally. Multiple doses.
Oral brequinar will be administered twice-weekly. After the first cohort of 6 subjects, dose adjustments can occur every 14-day cycle both at the intra-subject and the inter-cohort level depending on safety, efficacy, and biomarker levels.
Brequinar + Ribavirin
Subjects in Cohort 2 may roll over to add ribavirin dosing; subjects in Cohort 3 will start with brequinar alone then add ribavirin dosing.
Drug: Brequinar + Ribavirin
Cohort 2 subjects start dosing with brequinar alone twice weekly and may roll over into brequinar twice weekly + ribavirin BID. Cohort 3 subjects start with brequinar alone twice weekly then add ribavirin dosing BID.
- Number of Participants with Treatment-Related Adverse Events [ Time Frame: 12 months ]The number of subjects with treatment-related adverse events as assessed by CTCAE v. 4.03.
- Overall Response Rate (ORR) [ Time Frame: 12 months ]The number of participants in the Efficacy Analysis Set with best overall response of one of the responses of CR, CRi, CRh, PR, of MLFS.
- Complete Remission (CR) rate [ Time Frame: Up to approximately 12 months ]The proportion of subjects in the Efficacy Analysis Set with best overall response of CR
- Complete Remission with Incomplete Hematologic Recovery (CRi) rate [ Time Frame: Up to approximately 12 months ]The proportion of subjects in the Efficacy Analysis Set with a best overall response of CRi
- Complete Remission with Partial Hematological Recovery (CRh) rate [ Time Frame: Up to approximately 12 months ]The proportion of subjects in the Efficacy Analysis Set with a best overall response of CRh
- Morphologic Leukemia Free State (MLFS) rate [ Time Frame: Up to approximately 12 months ]The proportion of subjects in the Efficacy Analysis Set with a best overall response of MLFS
- Partial Remission (PR) rate [ Time Frame: Up to approximately 12 months ]The proportion of subjects in the Efficacy Analysis Set with a best overall response of PR
- Event free survival (EFS) rate [ Time Frame: Up to approximately 12 months ]Interval between first dose and relapse (>=5% bone marrow blasts, reappearance of blasts in blood, or development of extramedullary disease), disease progression, or both
- Duration of response [ Time Frame: Up to approximately 12 months ]The duration of response is defined as the number of days from the time response criteria are initially met for CR, CRi, CRh, PR, or MLFS (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, or death due to any cause. Participants without events reported are censored at the last disease evaluation.
- Brequinar Pharmacokinetics - Elimination Half-Life (T 1/2) [ Time Frame: Up to 14 days after first dose. ]The period of time required for the concentration of drug in plasma to be reduced by one-half.
- Brequinar Pharmacokinetics - AUC [ Time Frame: Up to 14 days after first dose. ]The plot of drug concentration in blood plasma vs. time.
- DHO Plasma Level [ Time Frame: Up to 14 days after first dose. Pre-dose at the beginning of each cycle (every 2 weeks for 3 months then every 4 weeks). ]Plasma level of DHO
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): NCT03760666
|Contact: Barbara L Powers, MSN, PhD||(617) firstname.lastname@example.org|
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Amandeep Salhotra, MD 626-256-4673 email@example.com|
|Principal Investigator: Amandeep Salhotra, MD|
|United States, Massachusetts|
|Massachusetts General Hospital||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Amir T Fathi, MD 617-724-1124 firstname.lastname@example.org|
|Principal Investigator: Amir Fathi, MD|
|Beth-Israel Deaconess Medical Center||Withdrawn|
|Boston, Massachusetts, United States, 02215|
|Dana Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Eric S Winder, MD 617-632-1906 email@example.com|
|Principal Investigator: Eric S Winer, MD|
|United States, Ohio|
|Cleveland Clinic Lerner College of Medicine||Recruiting|
|Cleveland, Ohio, United States, 44195|
|Contact: Hetty E. Carrawy, MD 216-445-5898 firstname.lastname@example.org|
|Principal Investigator: Hetty E. Carrawy, MD|
|United States, Texas|
|The University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Courtney DiNardo, MD 713-794-1141 email@example.com|
|Principal Investigator: Courtney DiNardo, MD|