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RECRUITINGPHASE1

Study of Oral PCLX-001 in R/R Acute Myeloid Leukemia

A Phase 1 Study of Oral PCLX-001 in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

NCT06613217•Pacylex Pharmaceuticals

Summary

This is a dose-finding study of oral zelenirstat (PCLX-001) in patients with R/R AML. There are two parts to the study: Dose Escalation and Dose Expansion.

Detailed Description

This is a dose-finding study of oral PCLX-001 in patients with R/R AML. There are two parts to the study: Dose Escalation and Dose Expansion. Dose Escalation will determine the minimum safe and biologically-effective dose of daily oral PCLX-001 in patients with R/R AML. The Bayesian optimal interval (BOIN) design will be used for dose escalation, informed by real-time assessment of safety, efficacy, PK and PD in each dose cohort. A maximum of 15 patients will enroll in the dose escalation part. Oral PCLX-001 will be provided as continuous daily dosing on a 28-day cycle. The starting dose will be 40 mg. AML patients will be evaluated for toxicity, PK, and the relationship between PK observed in this AML trial with universally co-administered CYP3A inhibitor drugs (as in this setting, azole antifungals are continuously administered to this population), in comparison with PK data derived from patients with NHL and solid tumors without co-administered CYP3A inhibitors. These data will be integrated to inform the decision on the minimum safe and biologically-effective dose to be used in the expansion cohort. PCLX-001 will be administered as an oral daily dose on a 28-day cycle as per the dose level schedule below. Dose Escalation Schedule: (1 cycle = 28 days) 1. Daily oral dose of 40mg 2. Daily oral dose of 70mg 3. Daily oral dose of 100mg 4. Daily oral dose of 140mg 5. Daily oral dose of 210mg 6. Daily oral dose of 280mg Trial will start at 40mg based on results from an ongoing independent dose escalation trial in NHL and solid tumors. If DLT is not observed at the dose of 280 mg, this dose will be considered the minimum safe and biologically-effective dose to be used in the expansion cohort. Dose expansion. 20 evaluable patients will be accrued and treated with the minimum safe and biologically-effective dose. PCLX-001 will be administered as an oral daily dose on a 28-day cycle to determine the safety and preliminary clinical activity of PCLX-001. Dosing Administration PCLX-001 will be administered orally, once daily, on 28-day cycles, at the same time each day.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•\-
•1. Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained before any study-specific procedures are performed.
•2. Male or female patients aged ≥ 18 years
•3. A diagnosis of AML as per 2016 WHO classification (Arber et al, 2016)
•4. Patients must have received at least one prior therapy for AML
•5. Patient must not be eligible for other therapies expected to provide clinical benefit
•6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix A).
•7. The use of chemotherapeutic or anti-leukemic agents is not permitted during the study with the following exceptions: (1) intrathecal (IT) therapy for patients with controlled CNS leukemia at the discretion of the Investigator. 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. (2) Use of 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.
•8. Patients must have adequate liver function as assessed by the following laboratory tests to be conducted within 7 (±3) days before the first dose of study drug:
•1. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) unless increase is due to hemolysis or congenital disorder such as Gilbert's syndrome
+14 more criteria

Exclusion Criteria

•\-
•1. Acute promyelocytic leukemia.
•2. Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study
•3. History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class \> II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months before study entry), myocardial infarction within the past 6 months before study entry, or uncontrolled cardiac arrhythmias
•4. Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion)
•5. Moderate or severe hepatic impairment, i.e., Child-Pugh class B or C
•6. Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ counts/levels \> 250, no history of AIDs-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on same anti-HIV retroviral medications.
•7. Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator's discretion provided that the disease is stable and sufficiently controlled under treatment.
•8. Infections of CTCAE Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade \> 2
•9. Uncontrolled seizure disorder requiring therapy with strong CYP3A4 inducers such as carbamazepine and phenytoin
+12 more criteria

Locations (1)

MD Anderson Cancer Centre

Houston, Texas, United States

Key Dates

Start Date

March 3, 2025

Primary Completion Date

March 1, 2026

Completion Date

September 1, 2026

Last Updated

March 10, 2025

Enrollment

ESTIMATED participants

Conditions

Relapsed Adult AML

Interventions

zelenirstat

DRUG

Contacts

Pacylex Pharmaceuticals

CONTACT

1 (888) 580-4483 info@pacylex.com

Heit, MSc

CONTACT

1 (888) 580-4483 ryan.heit@pacylex.com

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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: March 10, 2025Data 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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Study of Oral PCLX-001 in R/R Acute Myeloid Leukemia

Inclusion Criteria

Exclusion Criteria

Specialty Compared to Oncology Delivered Palliative Care for Patients With Acute Myeloid Leukemia

Dose-Escalation Study of Oral Administration of LP-108 as Monotherapy and in Combination With Azacitidine in Patients With Relapsed or Refractory MDS, CMML, or AML

Venetoclax-Navitoclax With Cladribine-based Salvage Therapy in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Pracinostat and Gemtuzumab Ozogamicin (PraGO) in Patients With Relapsed/Refractory Acute Myeloid Leukemia