Zelenirstat for Acute Myeloid Leukemia

Overseen By Pacylex Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pacylex Pharmaceuticals

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Cardiac disease, Uncontrolled hypertension, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a new oral treatment called zelenirstat (also known as PCLX-001) for individuals with acute myeloid leukemia (AML) that has recurred or not responded to other treatments. The main goal is to determine the optimal dose among several options to ensure safety and effectiveness. This trial suits those who have undergone at least one previous treatment for AML without success with other available therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not allow the use of chemotherapeutic or anti-leukemic agents during the study, except for specific cases like intrathecal therapy for controlled CNS leukemia and hydroxyurea for rapidly proliferative disease. Other medications are not mentioned, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that zelenirstat, the treatment under study, was well-tolerated in earlier studies. Patients took zelenirstat as a pill, and it was generally well-received up to the recommended dose for future trials. No serious safety concerns emerged at these levels. While the full effects of zelenirstat are still under investigation, early results regarding its safety in humans have been positive. As this is an early-phase trial, the main goal is to find the best dose, but existing data indicates it has been tolerated without major issues so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Most treatments for acute myeloid leukemia (AML) involve chemotherapy drugs like cytarabine and daunorubicin, which target rapidly dividing cells. However, Zelenirstat offers a new approach by targeting specific cellular pathways, potentially leading to fewer side effects and better outcomes. Researchers are excited about Zelenirstat because it could provide a more targeted therapy that is less harsh on the body, with dosing flexibility that allows for gradual adjustment based on patient tolerance. This treatment's novel mechanism and customizable dosing make it a promising alternative to traditional chemotherapy.

What evidence suggests that zelenirstat might be an effective treatment for acute myeloid leukemia?

Research has shown that zelenirstat may help treat acute myeloid leukemia (AML). In animal studies, zelenirstat significantly reduced the number of leukemia cells and destroyed leukemia stem cells, the source of the disease. Lab tests demonstrated that zelenirstat treatment led to over a 70% decrease in leukemia cell survival. Early human trials for other cancers found zelenirstat to be safe and somewhat effective. In this trial, participants will receive varying doses of zelenirstat to evaluate its safety and effectiveness in treating AML. These findings suggest that zelenirstat could be a promising treatment for AML. ^{1 2 3 4 5}

Who Is on the Research Team?

Naveen Pemmaraju

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory Acute Myeloid Leukemia (R/R AML) who have tried at least one other therapy and are not eligible for treatments expected to help them. They must be able to understand the study, sign consent, have certain liver function test levels, and an ECOG performance status of 0-2.

Inclusion Criteria

My heart is functioning well.

My liver is working well.

Agreement to use adequate contraception during and after the study period

Exclusion Criteria

I have an active hepatitis B or C infection.

I am currently receiving radiation or cancer treatment for another cancer.

Known hypersensitivity to study drugs or excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Determine the minimum safe and biologically-effective dose of daily oral PCLX-001 in patients with R/R AML using a Bayesian optimal interval design

28-day cycles, up to 18 months

Continuous daily dosing

Dose Expansion

Treat 20 evaluable patients with the minimum safe and biologically-effective dose to determine safety and preliminary clinical activity

28-day cycles, up to 18 months

Continuous daily dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PCLX-001

Trial Overview The study tests different doses of a new oral drug called zelenirstat (PCLX-001) in two parts: finding the right dose and then seeing how well it works at that dose. It's focused on patients whose AML has come back or hasn't responded to treatment.

How Is the Trial Designed?

Group I: zelenirstat intervention in R/R AML at 70mg daily Experimental Treatment 1 Intervention

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.

Group II: zelenirstat intervention in R/R AML at 40mg daily Experimental Treatment 1 Intervention

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.

Group III: zelenirstat intervention in R/R AML at 280mg daily (if needed) Experimental Treatment 1 Intervention

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.

Group IV: zelenirstat intervention in R/R AML at 210mg daily (if needed) Experimental Treatment 1 Intervention

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.

Group V: zelenirstat intervention in R/R AML at 140mg daily Experimental Treatment 1 Intervention

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.

Group VI: zelenirstat intervention in R/R AML at 100mg daily Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Pacylex Pharmaceuticals

Lead Sponsor

Trials

2

Recruited

100+

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11327210/

A first-in-human phase I trial of daily oral zelenirstat, a N ... In murine tail-vein injection models of human AML, zelenirstat reduced the leukemic cell burden and dramatically reduced the human leukemic ...

2. targetedonc.com targetedonc.com/view/phase-1-2-trial-of-oral-zelenirstat-launches-in-relapsed-refractory-aml

Phase 1/2 Trial of Oral Zelenirstat Launches in Relapsed ... “Our phase 1 dose escalation safety and tolerability study in solid tumor and lymphoma patients showed excellent safety and signs of efficacy ...

3. pacylex.reportablenews.com pacylex.reportablenews.com/pr/pacylex-publishes-phase-1-safety-and-efficacy-of-zelenirstat-in-cancer-patients-in-the-journal-investigational-new-drugs

Pacylex Publishes Phase 1 Safety and Efficacy of ... In AML models, zelenirstat preferentially killed leukemic stem enriched cell populations and reduced the bone marrow leukemic burden.

4. aacrjournals.org aacrjournals.org/mct/article/24/1/69/750661/Zelenirstat-Inhibits-N-Myristoyltransferases-to

Zelenirstat Inhibits N-Myristoyltransferases to Disrupt Src ... The cells were treated with zelenirstat for 96 hours, after which viability was measured. AML cell lines and primary patient cells underwent >70% viability loss ...

5. cancer.gov cancer.gov/clinicaltrials/NCI-2025-02082

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