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

NCT04022785 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2018-0725NCI-2019-02517P30CA016672
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 5 years

• 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.

  Up to 28 days

Secondary Outcomes (7)

• Overall response rate

  Within 3 months of treatment initiation

• Gene mutations in acute myeloid leukemia

  Up to 5 years

• Duration of response

  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

• Event-free survival

  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

• Overall survival

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

Study Arms (1)

Treatment (BRD4 Inhibitor PLX51107, azacitidine)

EXPERIMENTAL

Patients 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.

Drug: Azacitidine; Drug: BRD4 Inhibitor PLX51107

Interventions

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Treatment (BRD4 Inhibitor PLX51107, azacitidine)

BRD4 Inhibitor PLX51107 DRUG

Given PO

Also known as: PLX 51107, PLX-51107, PLX51107

Treatment (BRD4 Inhibitor PLX51107, azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders

Interventions

Azacitidine; PLX51107

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Naveen Pemmaraju

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2019
• First Posted: July 17, 2019
• Study Start: September 9, 2019
• Primary Completion: October 24, 2022
• Study Completion: October 24, 2022
• Last Updated: October 31, 2022

Record last verified: 2022-10

Locations

US (1)