Testing the Safety of Anti-Cancer Drug, CX-5461 (Pidnarulex), in Treating Lymphoma With Specific Changes in the MYC Gene
Phase 1b/2 Trial of Pidnarulex in MYC Aberrant Lymphoma
3 other identifiers
interventional
50
1 country
4
Brief Summary
This phase Ib/II trial tests the safety, side effects, best dose and how well giving CX-5461 works for the treatment of patients with B-cell non-Hodgkin lymphoma. CX-5461 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CX-5461 may be safe, tolerable and/or effective in treating patients with B-cell non-Hodgkin lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Oct 2026
Typical duration for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 16, 2025
CompletedFirst Posted
Study publicly available on registry
July 17, 2025
CompletedStudy Start
First participant enrolled
October 13, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
January 31, 2030
Study Completion
Last participant's last visit for all outcomes
January 31, 2030
April 28, 2026
April 1, 2026
3.3 years
July 16, 2025
April 25, 2026
Conditions
Outcome Measures
Primary Outcomes (5)
Incidence of adverse events (Phase 1)
Assessed by the Common Terminology Criteria for Adverse Events version 5. Safety will be summarized overall, by actual dose level in Phase 1b.
Up to 30 days after last dose of study treatment
Recommended phase 2 dose (RP2D) (Phase 1)
Up to 5 years
Pharmacokinetic (PK) levels (Phase 1)
Assessed using Liquid Chromatography Mass Spectrometry (LC-MS).
At cycle (C) 1 day (D) 8 at pre-dose, end of infusion, and 2 hours (hrs) post-dose; on C1D9 at 24 hrs post C1D8 infusion; on C1D10 at 48 hrs post C1D8 infusion; on C1D11 at 72 hrs post C1D8 infusion; and on C1D15 at 167 hrs post C1D8 infusion
Gene expression (Phase 1)
Assessed by ribonucleic acid sequencing complemented by whole exome sequencing using an average absolute log2 fold change relative to baseline with a significance threshold of p \< 0.05.
At baseline, C1D9 or C1D10 (within 24-48 hrs of C1D8 dosing),and at progression
Overall response rate (Phase 2)
Assessed using standard radiographic criteria according to Lugano criteria. Phase 2 results will be reported at the RP2D.
Up to 5 years
Secondary Outcomes (1)
Response to therapy (Phase 1 and 2)
Up to 5 years
Other Outcomes (2)
Circulating tumor deoxyribonucleic acid sequencing (Phase 1 and 2)
At baseline, day 21 of cycle 1, and complete remission
PK levels of cerebrospinal fluid (Phase 1 and 2)
At C1D8 2 hours post dose
Study Arms (1)
Treatment (CX-5461)
EXPERIMENTALPatients receive CX-5461 IV over 60 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture with CSF collection on study and PET scan/CT scan, tumor biopsy, and blood sample collection throughout the study.
Interventions
Undergo PET/CT scan
Undergo PET/CT scan
Given IV
Undergo CSF and blood sample collection
Undergo tumor biopsy
Eligibility Criteria
You may qualify if:
- Patients must have one of the following subtypes of aggressive B-cell non-Hodgkin lymphomas: double-expressor lymphoma (DEL), high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangement, or Burkitt lymphoma (BL). Eligible patients must have received at least two prior lines of treatment for diffuse large B-cell lymphoma (DLBCL) or at least one prior line of therapy for Burkitt Lymphoma and must have disease for which no standard curative or palliative treatment options exist or remain effective (Quin et al., 2016)
- Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of CX-5461 (Pidnarulex) in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%). ECOG 3 is allowed if directly related to lymphoma per treating provider
- Absolute neutrophil count ≥ 1,000/mcL
- Platelets ≥ 50,000/mcL
- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
- Patients with documented Gilbert's syndrome may be included if total bilirubin is ≤ 3 × ULN and direct bilirubin is within normal limits
- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional upper limit of normal (ULN)
- Glomerular filtration rate (GFR) ≥ 60 mL/min/, calculated by multiplying the estimated (e)GFR (mL/min/1.73 m\^2) by the individual's body surface area (BSA, calculated using an accepted formula) and dividing by 1.73 m\^2
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
- Patients with cytopenia related to abnormal bone marrow function in the setting of bone marrow involvement with lymphoma or post chimeric antigen receptor (CAR) T-cell are allowed to enroll if deemed safe by treating provider
- +4 more criteria
You may not qualify if:
- Patients must have recovered from clinically significant adverse events (AEs) of their most recent cancer immunotherapy to grade 1 or less (with the exception for alopecia or lymphopenia)
- Eligibility of subjects receiving any medications or substances known to affect or with the potential to affect the activity of CX-5461 (Pidnarulex) will be determined based on their potential to interact with the CYP3A4 isozyme. Specifically, subjects taking strong CYP3A4 inhibitors or strong CYP3A4 inducers will be excluded from participation in the trial. For medications or substances not listed, or in cases of uncertainty, the Principal Investigator may consult with a medical expert or a pharmacologist to make an informed decision regarding eligibility
- Patients with a baseline corrected QT (QTc) interval \> 480 msec
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CX-5461 (Pidnarulex)
- Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- Pregnant women are excluded from this study because CX-5461 (Pidnarulex) is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with CX-5461 (Pidnarulex), breastfeeding should be discontinued if the mother is treated with CX-5461 (Pidnarulex)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sami Ibrahimi
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 16, 2025
First Posted
July 17, 2025
Study Start (Estimated)
October 13, 2026
Primary Completion (Estimated)
January 31, 2030
Study Completion (Estimated)
January 31, 2030
Last Updated
April 28, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.