Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma

NCT05755087 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-21359NCI-2023-00200
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of tegavivint in treating patients with large b-cell lymphomas that has come back (relapsed) or does not respond to treatment (refractory). Tegavivint may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving tegavivint may help control the disease.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type; Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Refractory Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type; Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements; Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements; Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type; Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicity

  1\) To be declared as dose-limiting toxicity, an adverse event must be related (definite, probable, or possible) to study treatment during the first cycle of therapy only (first 28 days). Any death at least possibly related to tegavivint will be a DLT. No DLTs observed thus far.

  At the end of Cycle 1 (each cycle is 28 days)

• Maximum tolerated dose (MTD) for tegavivint

  Determination of the MTD of tegavivint using a 3+3 design.

  At the end of Cycle 1 (each cycle is 28 days)

• Determination of the recommended phase II dose (RP2D) of tegavivint

  2\) This study uses a traditional "3+3" designs. We therefore anticipate a total sample size of 12 with the maximum expected sample size of 24. Primary endpoint not yet reached.

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (6)

• Overall response rate (ORR)

  After cycle 2 (each cycle is 28 days) or end of treatment

• Complete response (CR) rate

  At the end of Cycle 2 (each cycle is 28 days)

• Duration of response (DOR)

  Time from the date of first response until the first date of progression or death from any cause, assessed up to 2 years from study enrollment

• Progression-free survival (PFS)

  Time from the date of first treatment until the first date of progression or death from any cause, assessed up to 2 years from study enrollment

• Event-free survival (EFS)

  Time from the date of first treatment until the first date of progression, re-treatment of lymphoma after initial immune-therapy, or death from any cause, assessed up to 2 years from study enrollment

Other Outcomes (7)

• Pharmacokinetic (PK) analysis AUC0-t

  Up to 14 weeks

• Pharmacokinetic (PK) analysis AUC0-infinity

  Up to 14 weeks

• Pharmacokinetic (PK) analysis Tmax

  Up to 14 weeks

Study Arms (1)

Treatment (Tegavivint)

EXPERIMENTAL

Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET and undergo blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and aspirate during screening and on the trial.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Drug: Tegavivint; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration

Interventions

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Also known as: Biopsy of bone marrow, Biopsy, Bone marrow

Treatment (Tegavivint)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspiration

Treatment (Tegavivint)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Tegavivint)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (Tegavivint)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (Tegavivint)

Tegavivint DRUG

Given IV

Also known as: BC 2059, BC-2059, BC2059, Tegatrabetan

Treatment (Tegavivint)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• One of the following three conditions:
• Relapsed/refractory histologically confirmed germinal center B-cell-like (GCB) and non-GCB diffuse large B cell lymphoma (DLBCL) with the following features:
• Increased expression of MYC (\>= 40%) and BCL2 (\>= 50%) by immunohistochemistry (IHC) or
• Presence of isolated MYC translocation Or
• Relapsed/refractory histologically confirmed high-grade B-cell lymphoma (HGBCL) (double hit \[DH\] and triple hit \[TH\]) with translocations of MYC and BCL2 and/or BCL6 Or
• Histologic transformation of indolent non-Hodgkin's lymphoma (NHL) to DLBCL
• Presence of BCL2 translocation with increased expression of MYC (≥40%) with or without MYC translocation
• Patients must have had at least two prior systemic therapies
• Patients must be ineligible for or refused autologous or allogenic hematopoietic stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy. Prior autologous stem cell transplant and/or CAR-T are allowed, if received \>= 3 months prior to enrollment
• Age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patients must have radiographically measurable disease by standard positron emission tomography (PET) uptake with at least one site of measured disease by standardized uptake value (SUV)
• Absolute neutrophil count (ANC) ≥ 500/mcL
• Platelet count ≥ 25,000/mcL
• Total bilirubin =\< 1.5 x the upper limit of the normal range (ULN)

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tegavivint or other agents used in study
• Known active central nervous system (CNS) lymphoma, history of CNS involvement allowed if in remission for \>= 3 months
• Evidence of chronic active Hepatitis B, chronic active Hepatitis C infection
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy (e.g., strong CYP3A inhibitors and/or concomitant medications that are excluded) are ineligible because of the potential for pharmacokinetic interactions with tegavivint
• Known history of active TB (Bacillus Tuberculosis)
• Major surgery within 3 weeks prior to start of study treatment
• Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality or corrected QT interval (QTc) \> 480 msec
• Uncontrolled concurrent illness including, but not limited to: ongoing or active infection (Viral, bacterial, fungal or other)
• Psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant and breastfeeding women are excluded from this study. The effects of tegavivint on the developing human fetus have the potential for teratogenic or abortifacient effects. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tegavivint
• Patients with abnormal serum chemistry values other than the specific limits detailed above, that in the opinion of the investigator is considered to be clinically significant, should be discussed with the Study PI before being enrolled in the study
• Personal history of malignancy except:
• Cervical intraepithelial neoplasia;
• Skin basal cell carcinoma;
• Treated localized prostate carcinoma with prostate specific antigen (PSA) \<1 ng/mL or untreated indolent prostate cancer

Sponsors & Collaborators

• Lapo Alinari: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; Biopsy

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Lapo Alinari, MD, PhD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 1, 2023
• First Posted: March 6, 2023
• Study Start: March 6, 2023
• Primary Completion (Estimated): March 5, 2028
• Study Completion (Estimated): March 5, 2028
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)