Acute Myelogenous LeukemiaPhase 1/2NCT02296242

Phase 1/2 Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes

A Phase 1/2 study testing BVD-523 in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by BioMed Valley Discoveries, Inc at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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). Read more about this study

Who is it for?: Ages 18 to 100 years
Conditions the study is for: Acute Myelogenous Leukemia, Myelodysplastic Syndrome
What is being tested?: BVD-523
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 53 participants
Where: 5 sitesUnited States
Study dates: Nov 2014to 15 Jun 2017
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 100 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 9Show fewer

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

Who cannot join

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

Show all 15Show fewer

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

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

United States5 sites

Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Roswell Park Cancer Institute
Buffalo, New York, 14263
MD Anderson Cancer Center
Houston, Texas, 77030
UCLA Medical Center
Los Angeles, California, 90024
Perelman Center for Advanced Medicine
Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

Read the detailed description

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.

Conditions: Acute Myelogenous Leukemia, Myelodysplastic Syndrome
Being tested: BVD-523
Medical subject headings: Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BVD-523Drug
Oral, multiple escalating doses, twice daily, for 21 days in each treatment cycle

Study groups in NCT02296242
Study group	Role	What they receive
BVD-523	Experimental	Not described Receives: Drug: BVD-523

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (2)

Clinical Evidence of Cancer Response in Bone Marrow Biopsies
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).
Measured: Until patient discontinuation; ~24 months on average
Duration of Disease Control in Patients That Respond
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.
Measured: Until patient discontinuation; ~24 months on average

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 201415 Jun 2017

First posted20 Nov 2014 (estimated)
Study startNov 2014
Primary completion15 Jun 2017
Study completion15 Jun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02296242
Sponsor's protocol ID: BVD-523-02
Other IDs: BVD-523-02
Status last verified: Jan 2019
First submitted: 13 Nov 2014
Last updated: 29 Jan 2019
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 28939558

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acute Myelogenous Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02296242
Acronym / sponsor ID: BVD-523-02
Conditions: Acute Myelogenous Leukemia, Myelodysplastic Syndrome
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: BioMed Valley Discoveries, IncIndustry (pharma, biotech, devices)
Study start: Nov 2014
Primary completion: 15 Jun 2017 (actual)
Study completion: 15 Jun 2017 (actual)
First posted: 20 Nov 2014 (estimated)
Results: Posted 5 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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).

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
BVD-523	Experimental	Drug: BVD-523

Who may qualify

Ages: 18 to 100 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Have either of the following diagnoses:
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

Key exclusion criteria (15 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BVD-523Oral, multiple escalating doses, twice daily, for 21 days in each treatment cycle	Drug	BVD-523

Primary outcome

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.

2 secondary outcomes

Clinical Evidence of Cancer Response in Bone Marrow Biopsies
Time frame: Until patient discontinuation; ~24 months on average
Duration of Disease Control in Patients That Respond
Time frame: Until patient discontinuation; ~24 months on average

Results and safety

Results posted to the registry on 5 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose-escalation 300mg b.i.d. Cohort	5	0
Dose-escalation 600mg b.i.d. Cohort	6	0
Dose-escalation 750mg b.i.d. Cohort	7	0
Cohort-expansion RAS(+) Group	14	0
Cohort-expansion RAS(-) Group	21	0

Primary outcome: Number of Patients With Dose Limiting Toxicities

Time frame: In the first 21 days of treatment. Count of participants. Unit: Participants

Measure	Dose-escalation 300mg b.i.d. Cohort n = 5	Dose-escalation 600mg b.i.d. Cohort n = 6	Dose-escalation 750mg b.i.d. Cohort n = 7	Cohort-expansion RAS(+) Group n = 14	Cohort-expansion RAS(-) Group n = 21
Any BVD-523-related DLTs?: Yes	0	0	2	0	0
Any BVD-523-related DLTs?: No	5	6	5	14	21
Related tox causing tx delay >4 days (rash >7days): Yes	0	0	2	0	0
Related tox causing tx delay >4 days (rash >7days): No	5	6	5	14	21

Dose-escalation 300mg b.i.d. Cohort vs Dose-escalation 600mg b.i.d. Cohort vs Dose-escalation 750mg b.i.d. Cohort: Highest dose (mg) with no DLTs.: 600

Primary outcome: 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. Mean (Standard Deviation). Unit: ng/mL

Measure	Dose-escalation 300mg b.i.d. Cohort n = 4	Dose-escalation 600mg b.i.d. Cohort n = 1	Dose-escalation 750mg b.i.d. Cohort n = 4	Cohort-expansion RAS(+) & RAS(-) Groups n = 12
0 hr (predose)	455 (212)	1860 (00)	2080 (1310)	1540 (800)
0.5 hr	428 (193)	1670 (00)	2020 (1240)	1280 (767)
1 hr	506 (159)	1590 (00)	2130 (693)	1440 (698)
2 hr	1300 (1090)	1760 (00)	2220 (1500)	1790 (776)
4 hr	1150 (555)	1520 (00)	2670 (1490)	1800 (914)
6 hr	728 (435)	1510 (00)	2360 (1510)	1400 (741)
8 hr	480 (301)	1100 (00)	1870 (1150)	1140 (623)
12 hr	528 (364)	902 (00)	1650 (1070)	974 (567)

Population analysed: The cohort-expansion patients were not separated by RAS status for the purposes of this assessment. Two patients in the cohort expansion had to have their dose reduced to 300mg BID and were analyzed separately (Cmax 1000 \& 1340 ng/mL on Day 22). 00 = not calculated (only 1 evaluable patient).

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: A treatment-emergent adverse event (TEAE) is any AE temporally associated with the use of BVD-523 from initiation of BVD-523 initiation until 30 calendar days following the last administration of BVD-523, whether or not the AE was considered related to study drug. TEAEs were monitored/assessed until 30 calendar days following the last administration of BVD-523.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose-escalation 300mg b.i.d. Cohort	5 of 5 (100%)	2 of 5 (40%)	4 of 5
Dose-escalation 600mg b.i.d. Cohort	4 of 6 (66.7%)	1 of 6 (16.7%)	2 of 6
Dose-escalation 750mg b.i.d. Cohort	6 of 7 (85.7%)	6 of 7 (85.7%)	4 of 7
Cohort-expansion RAS(+) Group	10 of 14 (71.4%)	9 of 14 (64.3%)	2 of 14
Cohort-expansion RAS(-) Group	18 of 21 (85.7%)	11 of 21 (52.4%)	4 of 21

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28939558Germann 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BVD-523 in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by BioMed Valley Discoveries, Inc at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Dose Limiting Toxicities (time frame: In the first 21 days of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02296242, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2019.