Recruiting
Phase 1
Phase 2

CX-5461

Sponsor:

National Cancer Institute (NCI)

Code:

NCT07069699

Conditions

Burkitt Lymphoma

Double-Expressor Lymphoma

High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Lumbar Puncture

Pidnarulex

Study Details

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.

Conditions

Burkitt Lymphoma

Double-Expressor Lymphoma

High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements

Study ID

NCT07069699

Start date

Oct 13, 2026

Status verified date

Apr, 2026

Completion date

Jan 31, 2030

Anticipated

Primary completion date

Jan 31, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • Patients without clinical evidence of central nervous system (CNS) lymphoma
  • The effects of CX-5461 (Pidnarulex) on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) 14 days prior to study entry and for the duration of study participation and for at least 6 months after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Women should not breastfeed while taking CX-5461 (Pidnarulex) and for 6 months after cessation of treatment. Men treated or enrolled on this protocol must also agree to use adequate contraception 14 days prior to the study, for the duration of study participation, and 6 months after completion of CX-5461 (Pidnarulex) administration. Women of childbearing age should not donate egg(s) and men should not donate sperm for the duration of study participation and 6 months after completion of the last dose CX-5461 (Pidnarulex)
  • Willingness to provide blood and biopsy samples for research purposes
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • 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)

Study Design

Enrollment

50 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (CX-5461)

Patients 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

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo CSF and blood sample collection

Computed Tomography

Undergo PET/CT scan

Lumbar Puncture

Undergo lumbar puncture

Pidnarulex

Given IV

Positron Emission Tomography

Undergo PET/CT scan

Primary outcome measure

  • Incidence of adverse events (Phase 1) [ Time Frame: Up to 30 days after last dose of study treatment ]
  • Recommended phase 2 dose (RP2D) (Phase 1) [ Time Frame: Up to 5 years ]
  • Pharmacokinetic (PK) levels (Phase 1) [ Time Frame: 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) [ Time Frame: At baseline, C1D9 or C1D10 (within 24-48 hrs of C1D8 dosing),and at progression ]
  • Overall response rate (Phase 2) [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Locations

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Nicole Foley

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Nicole Foley

University of Kansas Clinical Research Center

Recruiting

Fairway, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Aung M. Tun

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Aung M. Tun

University of Kansas Hospital-Indian Creek Campus

Recruiting

Overland Park, Kansas, United States, 66211

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Aung M. Tun

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Aung M. Tun

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777ou-clinical-trials@ouhsc.edu

Principal Investigator:

Sami Ibrahimi

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Jing-Zhou Hou

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Jul 31, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-07-31.