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PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome | Clinical Trials | Clareo Health

COMPLETEDPHASE1

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

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

NCT04022785•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

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. 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.

Detailed Description

PRIMARY OBJECTIVE: I. To determine the minimum safe and biologically-effective dose of the combination of PLX51107 and azacitidine (AZA). SECONDARY OBJECTIVES: I. 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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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
•* 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)
+9 more criteria

Exclusion Criteria

•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

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

September 9, 2019

Primary Completion Date

October 24, 2022

Completion Date

October 24, 2022

Last Updated

October 31, 2022

Enrollment

ACTUAL participants

Conditions

Acute Myeloid LeukemiaMyelodysplastic SyndromeMyelodysplastic/Myeloproliferative NeoplasmMyeloproliferative Neoplasm

Interventions

Azacitidine

DRUG

BRD4 Inhibitor PLX51107

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 31, 2022Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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

Inclusion Criteria

Exclusion Criteria

Phase I Study of HC-7366 for Acute Myeloid Leukemia

VAC Regimen for AML Patients Who Failed to Response to VA Regimen

A Study of Revumenib in R/R Leukemias Including Those With an MLL/KMT2A Gene Rearrangement or NPM1 Mutation

Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis

A Platform Protocol to Investigate Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies Undergoing Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Phase III Study of Induction and Consolidation Chemotherapy With Venetoclax in Patients With Newly Diagnosed AML or MDS-EB-2