Acute Graft Versus Host DiseasePhase 1/2NCT04910152

Novel BET Inhibitor PLX51107 for Steroid-Refractory Acute GVHD

A Phase 1/2 study testing BRD4 Inhibitor PLX51107 in people with Acute Graft Versus Host Disease and Steroid Refractory Graft Versus Host Disease, run by Hannah Choe, MD at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This phase Ib/II trial studies the side effects of PLX51107 in treating steroid-refractory acute graft versus host disease (GVHD). PLX51107 is a novel, potent non-benzodiazepine structured small molecule BET inhibitor with a unique binding mode selective for BRD4 inhibition and a more tolerable side effect profile. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Acute Graft Versus Host Disease, Steroid Refractory Graft Versus Host Disease
What is being tested?: BRD4 Inhibitor PLX51107
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteUnited States
Study dates: 19 Apr 2022to 28 Sep 2023
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age >= 18 years at the time of signing informed consent
Steroid-refractory acute GVHD as defined as progression of acute (a)GvHD within 3-5 days of therapy onset with >= 2 mg/kg/day of prednisone equivalent OR failure to improve within 5-7 days of treatment initiation with > 1-2 mg/kg/day of prednisone equivalent OR incomplete response after more than 28 days of immunosuppressive treatment including steroids
Recipients of ablative and reduced-intensity conditioning regimens
Recipients of human leukocyte antigen (HLA)-matched related and unrelated, 1-allele mismatched, haploidentical, or umbilical cord blood donor grafts
Prior lines of therapy for treatment of steroid-refractory acute GVHD are allowed. However, exposure to investigational therapies for the treatment of GVHD must be > 14 days or 5 half-lives (whichever is shorter) of first administration of study drug. For patients treated with ruxolitinib for the treatment of acute GVHD, ruxolitinib must be discontinued by at least one day prior to initiation of PLX51107
Eastern Cooperative Oncology Group (ECOG) performance status =< 3

Show all 10Show fewer

Absolute neutrophil count >= 1.0 x 10^9/L for 3 consecutive days). Use of growth factor support is allowed
Platelet count >= 50 x 10^9/L without transfusion support for 2 consecutive days
Women of child-bearing potential must have a negative serum pregnancy test at Screening and must agree to use an effective form of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drug. Effective forms of contraception include abstinence, hormonal contraceptive in conjunction with a barrier method, or a double barrier method. Women of non-child-bearing potential may be included if they are either surgically sterile or have been postmenopausal for >= 1 year
Fertile men must agree to use an effective method of birth control during the study and for up to 6 months after the last dose of study drug

Who cannot join

Prior exposure to a bromodomain inhibitor
Evidence of chronic GVHD
Evidence of active relapse of disease
Exposure to other investigational or anti-cancer therapies (not for GVHD) within 28 days or 5 half-lives (whichever is shorter) of first administration of study drug
Active, uncontrolled bacterial, fungal, or viral infection
Known or suspected allergy to the study drug

Show all 19Show fewer

Clinically significant cardiac disease, defined as:
Clinically significant cardiac arrhythmias, including bradyarrhythmia, and/or a need for anti-arrhythmic therapy (excluding beta blockers or digoxin). Individuals with controlled atrial fibrillation are not excluded
Fridericia-corrected QT interval (QTcF) >= 450 ms (male) or >= 470 ms (female) at screening
History of clinically significant cardiac disease or congestive heart failure greater than New York Heart Association Class II. Subjects must not have unstable angina (angina symptoms at rest) or experienced either new-onset angina within the last 3 months or myocardial infarction (MI) within the last 6 months unless it was due to the underlying disease and there has been appropriate revascularization. Individuals with ambiguous troponin levels that are not diagnostic of an MI should be discussed with the principal investigator (PI) prior to enrollment
Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before start of study medication (except for catheter-related venous thrombosis
Inability to take oral medication or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the Investigator, would preclude adequate absorption
Active thrombotic microangiopathy (TMA)
Women who are either pregnant or breast feeding
Measured or calculated (Cockcroft-Gault formula) creatinine clearance (CrCl) < 45 mL/min
Prothrombin time or international normalized ratio > 1.5 x upper limit of normal (ULN)
Activated partial thromboplastin time > 1.5 x ULN
Requiring mechanical ventilation or vasopressor support
Subject is participating in any other therapeutic clinical study (observational or registry studies are allowed)

Trial locations and contacts

1 site in 1 country.

United States1 site

Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Single Arm, Open Label, Phase 1b/2 Study of Novel BET Inhibitor PLX51107 for Steroid-Refractory Acute GVHD

Read the detailed description

PRIMARY OBJECTIVES:

To evaluate the safety and tolerability of BRD4 inhibitor PLX51107 (PLX51107) as a single agent for allogeneic transplant recipients with steroid-refractory acute graft versus host disease (GVHD).

II. To assess the pharmacokinetic (PK) and pharmacodynamic (PD) of orally administered PLX51107 in steroid-refractory acute GVHD patients.

SECONDARY OBJECTIVE:

To evaluate the preliminary efficacy of PLX51107 in steroid-refractory acute GVHD patients.

OUTLINE:

Patients receive BRD4 inhibitor PLX51107 orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then up to 6 months.

Conditions: Acute Graft Versus Host Disease, Steroid Refractory Graft Versus Host Disease
Being tested: BRD4 Inhibitor PLX51107

What participants receive

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

BRD4 Inhibitor PLX51107Drug
Also called PLX 51107, PLX-51107, PLX51107
Given PO

Study groups in NCT04910152
Study group	Role	What they receive
Treatment for aGVHD (BRD4 inhibitor PLX51107)	Experimental	Patients receive BRD4 inhibitor PLX51107 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: BRD4 Inhibitor PLX51107

What is being measured

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

Maximum Tolerated Dose (MTD)
Measured: Up to 28 days
Incidence of Adverse Events Grade 3 and 4
Adverse events by grade will be summarized. The occurrence of grade 3+ adverse events according to Common Terminology Criteria for Adverse Events will be summarized as well. Adverse events will initially be reviewed regardless of attribution, but also according to whether adverse events are possibly, probably, or definitely related to treatment.
Measured: Up to 6 months

Secondary outcomes (3)

Complete Response (CR)
The proportion of CR with a 95% confidence interval will be reported, assuming a binomial distribution.
Measured: At day 28
Overall Response Rate
The overall response rate (ORR) will include CR and partial response (PR), while mixed response (MR) and no response (NR) will be classified as no response. The ORR will be similarly analyzed as CR.
Measured: At day 28
Non-relapse Mortality (NRM)
The cumulative incidence curve accounting for competing risks will be generated to estimate the cumulative incidence of NRM rate at 6 months. The comparison in NRM between patient subgroups may be explored graphically.
Measured: From the date of starting PLX51107 to date of death with the competing risk as death due to disease, assessed at 6 months

Timeline

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

19 Apr 202228 Sep 2023

First posted2 Jun 2021
Study start19 Apr 2022
Primary completion28 Sep 2023
Study completion28 Sep 2023

Why it stopped: Sponsor decision

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 Graft Versus Host DiseaseStudies 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: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04910152
Sponsor's protocol ID: OSU-20273
Other IDs: NCI-2021-02282, R01CA252469
Status last verified: Jan 2025
First submitted: 24 Apr 2021
Last updated: 28 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Smith AL, Skupa SA, Eiken AP, Reznicek TE, Schmitz E, Williams N, Moore DY, D'Angelo CR, Kallam A, Lunning MA, Bociek RG, Vose JM, Mohamed E, Mahr AR, Denton PW, Powell B, Bollag G, Rowley MJ, El-Gamal D. BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia. JCI Insight. 2024 May 22;9(10):e177054. doi: 10.1172/jci.insight.177054.
PubMed 38775157

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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Study at a glance

From the registry record, last updated by the sponsor on 28 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Arm, Open Label, Phase 1b/2 Study of Novel BET Inhibitor PLX51107 for Steroid-Refractory Acute GVHD
ClinicalTrials.gov ID: NCT04910152
Acronym / sponsor ID: OSU-20273
Conditions: Acute Graft Versus Host Disease, Steroid Refractory Graft Versus Host Disease
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sponsor decision
Enrolment: 2 participants (actual)
Lead sponsor: Hannah Choe, MDUniversity, hospital or other
Collaborators: Plexxikon, National Cancer Institute (NCI)
Study start: 19 Apr 2022 (actual)
Primary completion: 28 Sep 2023 (actual)
Study completion: 28 Sep 2023 (actual)
First posted: 2 Jun 2021 (actual)
Results: Posted 28 Jan 2025

Clinical summary

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

Detailed description

PRIMARY OBJECTIVES:

To evaluate the safety and tolerability of BRD4 inhibitor PLX51107 (PLX51107) as a single agent for allogeneic transplant recipients with steroid-refractory acute graft versus host disease (GVHD).

II. To assess the pharmacokinetic (PK) and pharmacodynamic (PD) of orally administered PLX51107 in steroid-refractory acute GVHD patients.

SECONDARY OBJECTIVE:

To evaluate the preliminary efficacy of PLX51107 in steroid-refractory acute GVHD patients.

OUTLINE:

Patients receive BRD4 inhibitor PLX51107 orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then up to 6 months.

Study design

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

Arm	Type	Receives
Treatment for aGVHD (BRD4 inhibitor PLX51107)	Experimental	Drug: BRD4 Inhibitor PLX51107Patients receive BRD4 inhibitor PLX51107 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who may qualify

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

Key inclusion criteria (10 listed)

Age >= 18 years at the time of signing informed consent
Steroid-refractory acute GVHD as defined as progression of acute (a)GvHD within 3-5 days of therapy onset with >= 2 mg/kg/day of prednisone equivalent OR failure to improve within 5-7 days of treatment initiation with > 1-2 mg/kg/day of prednisone equivalent OR incomplete response after more than 28 days of immunosuppressive treatment including steroids
Recipients of ablative and reduced-intensity conditioning regimens
Recipients of human leukocyte antigen (HLA)-matched related and unrelated, 1-allele mismatched, haploidentical, or umbilical cord blood donor grafts
Prior lines of therapy for treatment of steroid-refractory acute GVHD are allowed. However, exposure to investigational therapies for the treatment of GVHD must be > 14 days or 5 half-lives (whichever is shorter) of first administration of study drug. For patients treated with ruxolitinib for the treatment of acute GVHD, ruxolitinib must be discontinued by at least one day prior to initiation of PLX51107

Key exclusion criteria (19 listed)

Prior exposure to a bromodomain inhibitor
Evidence of chronic GVHD
Evidence of active relapse of disease
Exposure to other investigational or anti-cancer therapies (not for GVHD) within 28 days or 5 half-lives (whichever is shorter) of first administration of study drug
Active, uncontrolled bacterial, fungal, or viral infection

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
BRD4 Inhibitor PLX51107Also: PLX 51107, PLX-51107, PLX51107Given PO	Drug	Treatment for aGVHD (BRD4 inhibitor PLX51107)

Primary outcome

Maximum Tolerated Dose (MTD)
Time frame: Up to 28 days
Incidence of Adverse Events Grade 3 and 4
Time frame: Up to 6 months
Adverse events by grade will be summarized. The occurrence of grade 3+ adverse events according to Common Terminology Criteria for Adverse Events will be summarized as well. Adverse events will initially be reviewed regardless of attribution, but also according to whether adverse events are possibly, probably, or definitely related to treatment.

3 secondary outcomes

Complete Response (CR)
Time frame: At day 28
Overall Response Rate
Time frame: At day 28
Non-relapse Mortality (NRM)
Time frame: From the date of starting PLX51107 to date of death with the competing risk as death due to disease, assessed at 6 months

Results and safety

Results posted to the registry on 28 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment for aGVHD (BRD4 Inhibitor PLX51107)	2	1

Primary outcome: Maximum Tolerated Dose (MTD)

Time frame: Up to 28 days

Population analysed: Maximum tolerated dose was not able to be determined due to low accrual number.

Primary outcome: Incidence of Adverse Events Grade 3 and 4

Time frame: Up to 6 months. Number. Unit: participants

Measure	Treatment for aGVHD (BRD4 Inhibitor PLX51107) n = 1
Grade 1 Adverse Events : Bloating	1
Grade 1 Adverse Events : Confusion	1
Grade 1 Adverse Events : Dyspnea	1
Grade 2 Adverse Events : Creatinine Increased	1
Grade 2 Adverse Events : Neutrophil Count Decreased	1
Grade 3 Adverse Events : Anemia	1
Grade 3 Adverse Events : Creatinine Increased	1
Grade 3 Adverse Events : Neutrophil Count Decreased	1

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Patients were evaluated for adverse events using the NCI CTCAE version 5.0 from the start of study up to 1 year, 5 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment for aGVHD (BRD4 Inhibitor PLX51107)	1 of 1 (100%)	1 of 1 (100%)	1 of 1

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38775157Smith AL, Skupa SA, Eiken AP, Reznicek TE, Schmitz E, Williams N, Moore DY, D'Angelo CR, Kallam A, Lunning MA, Bociek RG, Vose JM, Mohamed E, Mahr AR, Denton PW, Powell B, Bollag G, Rowley MJ, El-Gamal D. BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia. JCI Insight. 2024 May 22;9(10):e177054. doi: 10.1172/jci.insight.177054.
The JameslineLink provided by the sponsor.
Individual participant dataSharing planned: No

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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.

Hannah Choe, MD principal investigator

Ohio State University Comprehensive Cancer Center

1 site 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 BRD4 Inhibitor PLX51107 in people with Acute Graft Versus Host Disease and Steroid Refractory Graft Versus Host Disease, run by Hannah Choe, MD at 1 site 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 10 inclusion and 19 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: stopped early, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 28 Jan 2025). 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?

Maximum Tolerated Dose (MTD) (time frame: Up to 28 days). 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 NCT04910152, 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 28 Jan 2025.