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.
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
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
Single group
Biopsy Procedure
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo CSF and blood sample collection
Computed Tomography
Procedure/SurgeryUndergo PET/CT scan
Lumbar Puncture
Procedure/SurgeryUndergo lumbar puncture
Pidnarulex
DrugGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT scan
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.
Recommended phase 2 dose (RP2D) (Phase 1)
Pharmacokinetic (PK) levels (Phase 1)
Assessed using Liquid Chromatography Mass Spectrometry (LC-MS).
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.
Response to therapy (Phase 1 and 2)
Assessed according to Lugano criteria.
Circulating tumor deoxyribonucleic acid sequencing (Phase 1 and 2)
PK levels of cerebrospinal fluid (Phase 1 and 2)
Using LC-MS.
Click on the lead sponsor to view all of their trials.
