AzTrials
AzTrials

Relapsed Adult AMLPhase 1NCT06613217

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

A Phase 1 study testing zelenirstat in people with Relapsed Adult AML, run by Pacylex Pharmaceuticals at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Relapsed Adult AML
What is being tested?
zelenirstat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
3 Mar 2025to 1 Sep 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • -
  • The following inclusion criteria apply to ALL (dose escalation and dose expansion) patients:
  • 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
Show all 25Show fewer
  • 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
  • Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β- human chorionic gonadotropin (HCG)) pregnancy test obtained within 7 (±3) days before the start of administration of study drug.
  • Note: A woman is of childbearing potential, i.e., fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy.
  • Women of childbearing potential and fertile men must agree to use adequate contraception when sexually active from signing of the informed consent form for the full study until at least 6 months after the last study drug administration. Patients must agree to utilize 2 reliable and acceptable methods of contraception simultaneously. A man is considered fertile after puberty unless permanently sterile by bilateral orchiectomy. Men being treated with PCLX-001 are advised not to father a child during and up to 6 months after treatment; prior to treatment, advice should be sought for conserving sperm due to the chance of irreversible infertility as a consequence of treatment with PCLX-001. Female partners of childbearing potential from male study participants have to use adequate contraception / birth control between signing of the informed consent and 6 months after the last administration of the study drug if the male study participant is not sterilized. The investigator or a designated associate is requested to advise the patient how to achieve highly effective birth control. Highly effective (failure rate of less than 1% per year) contraception methods, when used consistently and correctly, include:
  • Combined (estrogen and progestin containing: oral, intravaginal transdermal and progestin-only (oral, injectable, implantable) hormonal contraception associated with inhibition of ovulation.
  • Intra-uterine device (IUD) or intrauterine hormone-releasing system (IUS).
  • Bilateral tubal occlusion or vasectomized partner (provided that partner is the sole sexual partner and has received medical assessment of the surgical success).
  • Sexual abstinence (reliability to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient).
  • Male patients with a female partner of reproductive potential must use a condom and ensure that an additional form of contraception is also used during treatment and until 6 months after last study drug administration. Patients must agree to utilize reliable and acceptable methods of contraception simultaneously.

Who cannot join

  • -
  • The following exclusion criteria apply to ALL (dose escalation and dose expansion) patients:
  • 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)
Show all 23Show fewer
  • 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.
  • Acute toxic effects (CTCAE Grade ≥2) of previous anticancer chemotherapy or immunotherapy that have not yet stabilized or if significant post-treatment toxicities have been observed. (Note however that toxic effects of previous anticancer therapy considered as chronic, such as chemotherapy-induced neuropathy, fatigue, alopecia, or anorexia of CTCAE Grade <2, for which further resolution is not expected, do not prevent participation in this study.)
  • Patients on active radiation therapy or active antineoplastic therapy for a concurrent malignancy at the time of screen. Maintenance therapy, hormonal therapy, or steroid therapy for well-controlled malignancy is allowed.
  • Previous assignment to treatment during this study
  • Concomitant participation in another clinical study with investigational medicinal product(s)
  • Substance abuse, medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Clinically relevant findings in the ECG such as a second- or third-degree atrioventricular block, prolongation of the QRS complex > 120 ms (except for bundle branch block pattern), or prolongation of the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise between the investigator and the sponsor's medically responsible person.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Pacylex Pharmaceuticals contact

1 (888) 580-4483

info@pacylex.com

Heit, MSc contact

1 (888) 580-4483

ryan.heit@pacylex.com

United States1 site, 1 recruiting

  • MD Anderson Cancer Centre

    Houston, Texas, 77030

    Naveen Pemmaraju, 713-792-4956, npemmaraju@mdanderson.org

    Recruiting

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
zelenirstat
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • zelenirstatDrug

    Also called PCLX-001

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

Study groups in NCT06613217
Study groupRoleWhat they receive
zelenirstat intervention in R/R AML at 40mg dailyExperimentalThree 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.
Receives: Drug: zelenirstat
zelenirstat intervention in R/R AML at 70mg dailyExperimentalThree 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.
Receives: Drug: zelenirstat
zelenirstat intervention in R/R AML at 100mg dailyExperimentalThree 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.
Receives: Drug: zelenirstat
zelenirstat intervention in R/R AML at 140mg dailyExperimentalThree 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.
Receives: Drug: zelenirstat
zelenirstat intervention in R/R AML at 210mg daily (if needed)ExperimentalThree 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.
Receives: Drug: zelenirstat
zelenirstat intervention in R/R AML at 280mg daily (if needed)ExperimentalThree 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.
Receives: Drug: zelenirstat

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 18 months

Secondary outcomes (1)

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

    Tumor response and progression of AML will be evaluated by the investigator at each study center.

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2024
  2. Study start3 Mar 2025
  3. Primary completion1 Mar 2026 (estimated)
  4. Study completion1 Sep 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06613217
Sponsor's protocol ID
PCLX-001-02
Status last verified
Mar 2025
First submitted
1 Aug 2024
Last updated
10 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33093447

  • 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.

    PubMed 35323358

  • 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.

    PubMed 38715059

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing zelenirstat in people with Relapsed Adult AML, run by Pacylex Pharmaceuticals at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Pacylex Pharmaceuticals (1 (888) 580-4483, info@pacylex.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine, during the dose escalation phase, the recommended dose of zelenirstat for the dose expansion phase of the trial. (time frame: Up to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06613217, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in