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Acute Myeloid LeukemiaPhase 1NCT04022785

PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

A Phase 1 study testing Azacitidine and BRD4 Inhibitor PLX51107 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site 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 phase I trial studies the side effects and best dose of PLX51107 and how well it works with azacitidine in treating patients with acute myeloid leukemia or myelodysplastic syndrome. PLX51107 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine and BRD4 Inhibitor PLX51107
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
9 Sep 2019to 24 Oct 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Diagnosis of
  • AML (World Health Organization [WHO] classification definition of >= 20% blasts), or
  • MDS intermediate-2 score or with > 10% blasts, to include: MDS, myeloproliferative neoplasm (MPN) with 10% blasts or more, or MDS/MPN 10% blasts or more
  • Patients who have received at least one prior therapy for AML or for MDS will be eligible. Any prior therapy for AML or MDS will be counted as a prior salvage
  • In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of protocol therapy will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for cytotoxic/non-cytotoxic agents. The half-life for the therapy in question will be based on published pharmacokinetic literature (abstracts, manuscripts, investigator brochures, or drug-administration manuals) and will be documented in the protocol eligibility document. The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions:
  • Intrathecal (IT) therapy for patients with controlled central nervous system (CNS) leukemia at the discretion of the principal investigator (PI). Controlled CNS leukemia is defined by the absence of active clinical signs of CNS disease and no evidence of CNS leukemia on the most recent 2 simultaneous cerebrospinal fluid (CSF) evaluations
Show all 19Show fewer
  • Use of one dose of cytarabine (up to 2 g/m^2) or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. These medications will be recorded in the case-report form.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Measured or calculated creatinine clearance >= 60 mL/min (unless considered due to leukemia)
  • Total bilirubin < 1.8 mg/dL (unless increase is due to hemolysis, congenital disorder, or leukemia)
  • Transaminases (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x upper limit of normal (ULN) (unless considered due to leukemia)
  • Potassium levels should be within institutional normal limits (unless considered due to leukemia)
  • Magnesium levels should be within institutional normal limits (unless considered due to leukemia)
  • Calcium (normalized for albumin) levels should be within institutional normal limits (unless considered due to leukemia)
  • Ability to take oral medication
  • Ability to understand and provide signed informed consent prior to any study-related procedures and to comply with all study requirements
  • Baseline left ventricular ejection fraction by echocardiogram (ECHO) or multigated acquisition scan (MUGA) >= 50%
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential
  • WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy until after the last dose of investigational drug. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) as well as men with azoospermia do not require contraception

Who cannot join

  • Patients with known significant impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PLX51107
  • Patients with any other known concurrent severe and/or uncontrolled medical condition including but not limited to diabetes, cardiovascular disease including hypertension, renal disease, or active uncontrolled infection, which could compromise participation in the study. Patients on active antineoplastic or radiation therapy for a concurrent malignancy at the time of screening. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed
  • Patients with known positive human immunodeficiency virus (HIV), hepatitis B or C infection by serology, with the exception of those with an undetectable viral load within 3 months. (HIV testing and hepatitis B or C testing is not required prior to study entry). Subjects with serologic evidence of prior vaccination to hepatitis B virus (HBV) (i.e., hepatitis B virus surface antigen negative [HBs Ag-], and hepatitis B surface antibody positive [HBs+]) may participate
  • Patients with advanced malignant hepatic tumors
  • Patients with known hypersensitivity to AZA or mannitol
  • Women who are pregnant or are breast-feeding
  • Patients who receive strong CYP3A4 and CYP2C8 inhibitors or inducers or CYP3A4 substrate drugs with a narrow therapeutic range, taken within 14 days or 5 drug half-lives, whichever is longer, before start of study drug
  • Patients who have received anti-cancer therapy within 14 days (or 5 half-lives) with all toxicities resolved to grade 1 or less. No immune therapy or other biologic therapy (other monoclonal antibodies or antibody-drug conjugates [ADCs]) within 28 days of cycle 1 day 1

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase I Study of PLX51107 (A Novel Bromodomain Inhibitor) in Combination With Azacytidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia (AML)

This phase I trial studies the side effects and best dose of PLX51107 and how well it works with azacitidine in treating patients with acute myeloid leukemia or myelodysplastic syndrome. PLX51107 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving PLX51107 and azacitidine may work better than azacitidine alone in treating patients with acute myeloid leukemia or myelodysplastic syndrome.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the minimum safe and biologically-effective dose of the combination of PLX51107 and azacitidine (AZA).

SECONDARY OBJECTIVES:

  1. To determine overall response rate (ORR) rate including CR (complete remission) + CRp (complete remission with incomplete platelet recovery) + CRi (complete remission with incomplete count recovery) + CRh (complete remission with partial hematologic recovery), partial remission (PR) within 3 months of treatment initiation of PLX51107 and AZA combination in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

II. To investigate correlations of response to this combination with a pre-therapy, on-therapy, and progression 81-gene panel of gene mutations in AML.

III. To determine the duration of response (DOR), event-free survival (EFS), overall survival (OS), and number of patients bridged to stem cell transplant (SCT) and median duration to SCT from the initiation of the combination.

OUTLINE: This is a dose-escalation study of PLX51107.

Patients receive PLX51107 orally (PO) once daily (QD) on days 1-21 and azacitidine subcutaneously (SC) or intravenously (IV) over 15 minutes on days 8-14 and 22-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, then every 6-12 months for 5 years.

Being tested
Azacitidine, BRD4 Inhibitor PLX51107
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Myeloproliferative Disorders

What participants receive

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

  • AzacitidineDrug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Given IV or SC

  • BRD4 Inhibitor PLX51107Drug

    Also called PLX 51107, PLX-51107, PLX51107

    Given PO

Study groups in NCT04022785
Study groupRoleWhat they receive
Treatment (BRD4 Inhibitor PLX51107, azacitidine)ExperimentalPatients receive PLX51107 PO QD on days 1-21 and azacitidine SC or IV over 15 minutes on days 8-14 and 22-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Azacitidine; Drug: BRD4 Inhibitor PLX51107

What is being measured

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

  1. Incidence of adverse events

    Toxicity type and severity will be summarized for each patient cohort using frequency tables. Per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.

    Measured: Up to 5 years

  2. Minimum safe and biologically effective dose

    The minimum safe and biologically-effective dose is the highest dose level in which < 2 patients of 6 develop first cycle dose limiting toxicity.

    Measured: Up to 28 days

Secondary outcomes (7)

  1. Overall response rate

    Will be defined as blast count reduction, hematologic improvement, partial remission, complete remission (CR), complete remission with incomplete count recovery, complete remission with incomplete platelet recovery, complete remission with partial hematologic recovery. Will be calculated and credible interval will be provided. Wilcoxon rank sum test or Fisher's exact test will be used to evaluate the association between patient prognostic factor (e.g. lab result and gene mutation) and response.

    Measured: Within 3 months of treatment initiation

  2. Gene mutations in acute myeloid leukemia

    Pre-therapy, on-therapy, and progression 81-gene panel of gene mutations will be correlated with response.

    Measured: Up to 5 years

  3. Duration of response

    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

    Measured: Number of days from the date of initial response to the date of first documented disease progression/relapse or death, whichever occurs first, assessed up to 5 years

  4. Event-free survival

    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

    Measured: Number of days from the date of treatment initiation to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first, assessed up to 5 years

  5. Overall survival

    Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.

    Measured: Time from treatment start until death or last follow up, assessed up to 5 years

  6. Number of patients bridged to stem cell transplant (SCT)

    Measured: Up to 5 years

  7. Median duration to SCT from initiation of combination

    Measured: Up to 5 years

Timeline

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

  1. First posted17 Jul 2019
  2. Study start9 Sep 2019
  3. Primary completion24 Oct 2022
  4. Study completion24 Oct 2022

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04022785
Sponsor's protocol ID
2018-0725
Other IDs
NCI-2019-02517, 2018-0725, P30CA016672
Status last verified
Oct 2022
First submitted
15 Jul 2019
Last updated
31 Oct 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azacitidine and BRD4 Inhibitor PLX51107 in people with Acute Myeloid Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center 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 19 inclusion and 8 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 31 Oct 2022. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Incidence of adverse events (time frame: Up to 5 years). 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 NCT04022785, 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 31 Oct 2022.

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