NCT02296242

Brief Summary

This study is being performed to assess the safety, tolerability, and preliminary clinical effects of BVD-523 given orally, twice daily for 21-day cycles, in patients with Acute Myelogenous Leukemia (AML) or Myelodysplastic Syndrome (MDS).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
53

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Nov 2014

Typical duration for phase_1

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2014

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

November 13, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 20, 2014

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 15, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 15, 2017

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

September 5, 2018

Completed
Last Updated

January 29, 2019

Status Verified

January 1, 2019

Enrollment Period

2.6 years

First QC Date

November 13, 2014

Results QC Date

June 28, 2018

Last Update Submit

January 9, 2019

Conditions

Acute Myelogenous LeukemiaMyelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

  • Number of Patients With Dose Limiting Toxicities

    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.

    In the first 21 days of treatment

  • Steady-state Plasma Concentration of BVD-523 and Selected Metabolites Over 12 Hours

    The PK population consisted of patients who received at least one dose of BVD-523 and had evaluable PK data in plasma.

    Samples will be collected on or about Day 22 of the protocol

Secondary Outcomes (2)

  • Clinical Evidence of Cancer Response in Bone Marrow Biopsies

    Until patient discontinuation; ~24 months on average

  • Duration of Disease Control in Patients That Respond

    Until patient discontinuation; ~24 months on average

Other Outcomes (1)

  • Pharmacodynamic Results of Inhibition (%) of Molecular Target (ERK Pathway) Assessed by Blood and Tissue Analyses.

    Patients will be evaluated at baseline and on or about Day 22 of the protocol

Study Arms (1)

BVD-523

EXPERIMENTAL
Drug: BVD-523

Interventions

BVD-523DRUG

Oral, multiple escalating doses, twice daily, for 21 days in each treatment cycle

BVD-523

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Have either of the following diagnoses:
  • Morphologically confirmed acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL), including leukemia secondary to prior therapy or antecedent hematologic disorder (e.g., MDS or myeloproliferative disorders), who have failed to achieve CR or who have relapsed after prior therapy and are not candidates for potentially curative therapy
  • Intermediate-2 or High-grade risk MDS (including chronic myelomonocytic leukemia (CMML))
  • Have received at least one prior therapy. Patients who are over age 65 and have not received therapy for AML are also eligible, if they are not candidates for induction chemotherapy
  • ECOG performance status of 0 to 2
  • Predicted life expectancy of ≥ 3 months
  • Adequate liver, renal and cardiac function
  • For Group 1 in Part 2 of the Study ONLY:
  • Positive for RAS mutation at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory prior to study entry

You may not qualify if:

  • Concomitant malignancies except carcinoma in situ, basal or squamous cell skin carcinoma; low grade prostate cancer treated with prostatectomy more than 10 years ago; early stage melanoma treated with complete surgical excision more than 5 years ago; carcinoma in situ of cervix treated with cone procedure more than 8 years ago
  • Gastrointestinal condition which could impair absorption of study medication
  • Uncontrolled or severe intercurrent medical condition
  • Patients with rapidly increasing peripheral blood blast counts
  • Known uncontrolled central nervous system involvement
  • Any cancer-directed therapy within 28 days or 5 half-lives, whichever is shorter
  • Any concurrent or prior use of an investigational drug (including MEK inhibitors) within previous 28 days or 5 half-lives, whichever is shorter
  • Received chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Received chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity within the last two weeks.
  • Ongoing anticoagulant therapy that cannot be held if necessary to permit bone marrow sampling.
  • Major surgery within 4 weeks prior to first dose
  • Pregnant or breast-feeding women
  • Any evidence of serious active infections
  • Any important medical illness or abnormal laboratory finding that would increase the risk of participating in this study
  • A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
  • Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, and CYP3A4, or strong inducers of CYP3A4

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

UCLA Medical Center

Los Angeles, California, 90024, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ. Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22.

    PMID: 28939558DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteMyelodysplastic Syndromes

Interventions

ulixertinib

Condition Hierarchy (Ancestors)

Leukemia, MyeloidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow Diseases

Results Point of Contact

Title
Dean Welsch, PhD
Organization
BioMed Valley Discoveries
dwelsch@biomed-valley.com
8163898831

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 13, 2014

First Posted

November 20, 2014

Study Start

November 1, 2014

Primary Completion

June 15, 2017

Study Completion

June 15, 2017

Last Updated

January 29, 2019

Results First Posted

September 5, 2018

Record last verified: 2019-01

Locations

US(5)