Phase 1/2 Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes
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|ClinicalTrials.gov Identifier: NCT02296242|
Recruitment Status : Completed
First Posted : November 20, 2014
Results First Posted : September 5, 2018
Last Update Posted : January 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myelogenous Leukemia Myelodysplastic Syndrome||Drug: BVD-523||Phase 1 Phase 2|
The study is being performed to assess the safety and tolerability of BVD-523 given orally, twice daily for 21-day cycles.
Part 1 of the study will establish dose limiting toxicities (DLT), maximum tolerated dose (MTD), and the recommended Phase 2 dose (RP2D).
In Part 2 of the study, additional patients with particular tumor types and/or cancers harboring specific genetic mutations will be recruited for treatment at the Recommended Phase 2 Dose (RP2D). Patients may also be assessed pharmacodynamic measures in healthy or malignant tissues, using biomarker assays for phosphorylation, cytotoxic or cytostatic measures.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 1/2 Dose-Escalation, Safety, Clinical Activity, Pharmacokinetic and Pharmacodynamic Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes|
|Study Start Date :||November 2014|
|Actual Primary Completion Date :||June 15, 2017|
|Actual Study Completion Date :||June 15, 2017|
Oral, multiple escalating doses, twice daily, for 21 days in each treatment cycle
- Number of Patients With Dose Limiting Toxicities [ Time Frame: In the first 21 days of treatment ]DLT defined using CTCAE v.4.03. All toxicities were considered to be related to BVD523 if not definitively explained by underlying disease, intercurrent illness, or con meds.
- Steady-state Plasma Concentration of BVD-523 and Selected Metabolites Over 12 Hours [ Time Frame: Samples will be collected on or about Day 22 of the protocol ]The PK population consisted of patients who received at least one dose of BVD-523 and had evaluable PK data in plasma.
- Clinical Evidence of Cancer Response in Bone Marrow Biopsies [ Time Frame: Until patient discontinuation; ~24 months on average ]Assessments were made via bone marrow biopsies using the International Working Group 2003 and 2006 criteria for AML or MDS, respectively. Bone marrow assessments (aspiration or biopsy, cytogenetics) were collected prior to therapy on Day 1 and Day 22, every 2 cycles thereafter, as well as at the final study visit if discontinuation was not due to disease progression. Some patients were unable to have bone marrow assessments taken at any or all of the time points. Shown is best response across all time points. Less than partial remission/response (<PR), partial remission/response (PR), complete remission/response with incomplete platelet recovery (CRp), or complete remission/response (CR).
- Duration of Disease Control in Patients That Respond [ Time Frame: Until patient discontinuation; ~24 months on average ]Assessments were made via bone marrow biopsies using the International Working Group 2003 and 2006 criteria for AML or MDS, respectively. Progression-free survival (PFS) and duration of response (DOR) of AML or MDS patients was assessed in patients treated with BVD-523 that achieved complete remission/response (CR) or complete remission/response with incomplete platelet recovery (CRp). <PR = less than partial remission/response. Shown is the duration (number of days) of CR or CRp response for the 2 patients in part 2 that obtained this level of response.
- Pharmacodynamic Results of Inhibition (%) of Molecular Target (ERK Pathway) Assessed by Blood and Tissue Analyses. [ Time Frame: Patients will be evaluated at baseline and on or about Day 22 of the protocol ]Multiple biomarkers intended to demonstrate inhibition of the molecular target, and mechanism of action were investigated from blood and/or bone marrow aspirate samples. Phosphorylation of ERK enzyme substrate proteins (e.g. RSK1 and RSK2 genes) were measured. Additional biomarkers, including PBMCs and/or DNA sequence analysis, were identified and measured as appropriate. Measurements were by ELISA. The pharmacodynamics (PD) population was defined as all patients who received at least one dose of study drug and had sufficient, valid PD samples to estimate key parameters for at least one of the days of sampling.
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): NCT02296242
|United States, California|
|UCLA Medical Center|
|Los Angeles, California, United States, 90024|
|United States, Georgia|
|Winship Cancer Institute of Emory University|
|Atlanta, Georgia, United States, 30322|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|United States, Pennsylvania|
|Perelman Center for Advanced Medicine|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|