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

NCT06613217 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PCLX-001-02
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Relapsed Adult AML

Outcome Measures

Primary Outcomes (1)

• To determine, during the dose escalation phase, the recommended dose of zelenirstat for the dose expansion phase of the trial.

  The recommended dose will be the dose level below that for the cohort in which maximum tolerated dose (MTD) was reached/exceeded. MTD will have been reached when 2 or more patients in a cohort experience DLT.

  Up to 18 months

Secondary Outcomes (1)

• To evaluate the clinical response rate in patients treated with zelenirstat with AML.

  Up to 18 months

Study Arms (6)

zelenirstat intervention in R/R AML at 40mg daily

EXPERIMENTAL

Three patients will be treated at 40 mg daily dose level. If 0/3 patients experience DLT, 3 patients will be treated at the next dose level.

Drug: zelenirstat

zelenirstat intervention in R/R AML at 70mg daily

EXPERIMENTAL

Three patients will be treated at 70 mg daily dose level. If 0/3 patients experience DLT, 3 patients will be treated at the next dose level.

Drug: zelenirstat

zelenirstat intervention in R/R AML at 100mg daily

EXPERIMENTAL

Three patients will be treated at 100 mg daily dose level. If 0/3 patients experience DLT, 3 patients will be treated at the next dose level.

Drug: zelenirstat

zelenirstat intervention in R/R AML at 140mg daily

EXPERIMENTAL

Three patients will be treated at 140 mg each dose level. If 0/3 patients experience DLT, 3 patients will be treated at the next dose level.

Drug: zelenirstat

zelenirstat intervention in R/R AML at 210mg daily (if needed)

EXPERIMENTAL

Three patients will be treated at 210 mg daily dose level. If 0/3 patients experience DLT, 3 patients will be treated at the next dose level.

Drug: zelenirstat

zelenirstat intervention in R/R AML at 280mg daily (if needed)

EXPERIMENTAL

Three patients will be treated at 280 mg daily dose level. If 0/3 patients experience DLT, 3 additional patients will be treated at the same dose and the study will be concluded.

Drug: zelenirstat

Interventions

zelenirstat DRUG

Zelenirstat will be administered orally, once daily, on 28-day cycles, at the same time each day.

Also known as: PCLX-001

zelenirstat intervention in R/R AML at 100mg daily; zelenirstat intervention in R/R AML at 140mg daily; zelenirstat intervention in R/R AML at 210mg daily (if needed); zelenirstat intervention in R/R AML at 280mg daily (if needed); zelenirstat intervention in R/R AML at 40mg daily; zelenirstat intervention in R/R AML at 70mg daily

Eligibility Criteria

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

You may qualify if:

• 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.
• Male or female patients aged ≥ 18 years
• A diagnosis of AML as per 2016 WHO classification (Arber et al, 2016)
• Patients must have received at least one prior therapy for AML
• Patient must not be eligible for other therapies expected to provide clinical benefit
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (Appendix A).
• 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.
• 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:
• 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
• ALT and AST ≤ 2.5 times ULN or ≤ 5 times ULN for patients with malignant liver involvement
• Patients must have adequate kidney function, as assessed by both:
• the estimated glomerular filtration rate (eGFR) \>60 mL/min within 7 (±3) days before the first dose of study drug (eGFR to be calculated by the Cockcroft-Gault formula)
• creatinine ≤ 1.5 times the ULN
• Adequate cardiac function per institutional normal measured by echocardiography or multi-gated acquisition (MUGA) scan (Left ventricular ejection fraction (LVEF) ≥ 50%)
• Ability to take oral medication

You may not qualify if:

• Acute promyelocytic leukemia.
• Known hypersensitivity to the study drugs or excipients of the preparations or any agent given in association with this study
• 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
• Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion)
• Moderate or severe hepatic impairment, i.e., Child-Pugh class B or C
• 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.
• 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.
• Infections of CTCAE Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade \> 2
• Uncontrolled seizure disorder requiring therapy with strong CYP3A4 inducers such as carbamazepine and phenytoin
• Previous or concurrent cancer that is distinct in primary site or histology from AML, with the exception of the following previous or concurrent cancer types:
• Curative treatment for localized cancer completed without signs of recurrence and treatment-related toxicity and low risk of recurrence as assessed by the investigator,
• In-situ prostate cancer, Gleason Score \<7, prostate-specific antigen \<10 ng/mL (very low risk and low risk, according to therapy guidelines, e.g., the National Comprehensive Cancer Network guideline; active surveillance / observation is a recommended option).
• Inability to swallow oral medications
• Any malabsorption condition that may significantly alter the absorption of PCLX-001.
• Breastfeeding. Female patients must not breastfeed during treatment and until 4 months after last study drug administration.

Sponsors & Collaborators

• Pacylex Pharmaceuticals: lead
• Ozmosis Research Inc.: collaborator
• United States Department of Defense: collaborator

Study Sites (1)

MD Anderson Cancer Centre

Houston, Texas, 77030, United States

RECRUITING

Related Publications (3)

• Beauchamp E, Yap MC, Iyer A, Perinpanayagam MA, Gamma JM, Vincent KM, Lakshmanan M, Raju A, Tergaonkar V, Tan SY, Lim ST, Dong WF, Postovit LM, Read KD, Gray DW, Wyatt PG, Mackey JR, Berthiaume LG. Targeting N-myristoylation for therapy of B-cell lymphomas. Nat Commun. 2020 Oct 22;11(1):5348. doi: 10.1038/s41467-020-18998-1.

  PMID: 33093447 BACKGROUND

• Sangha R, Davies NM, Namdar A, Chu M, Spratlin J, Beauchamp E, Berthiaume LG, Mackey JR. Novel, First-in-Human, Oral PCLX-001 Treatment in a Patient with Relapsed Diffuse Large B-Cell Lymphoma. Curr Oncol. 2022 Mar 13;29(3):1939-1946. doi: 10.3390/curroncol29030158.

  PMID: 35323358 BACKGROUND

• Beauchamp E, Gamma JM, Cromwell CR, Moussa EW, Pain R, Kostiuk MA, Acevedo-Morantes C, Iyer A, Yap M, Vincent KM, Postovit LM, Julien O, Hubbard BP, Mackey JR, Berthiaume LG. Multiomics analysis identifies oxidative phosphorylation as a cancer vulnerability arising from myristoylation inhibition. J Transl Med. 2024 May 7;22(1):431. doi: 10.1186/s12967-024-05150-6.

  PMID: 38715059 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Naveen Pemmaraju

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pacylex Pharmaceuticals

CONTACT

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

Heit, MSc

CONTACT

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

Study Design

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

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: September 25, 2024
• Study Start: March 3, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)