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

NCT ID: NCT05755087

Last Updated: 2025-11-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-06

Study Completion Date

2027-03-05

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of tegavivint in patients with relapsed/refractory c-Myc overexpressing large B-cell lymphoma.

II. To determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of tegavivint.

SECONDARY OBJECTIVES:

I. To determine the preliminary efficacy of tegavivint in patients with relapsed/refractory c-Myc overexpressing large B-cell lymphoma.

II. To determine the pharmacokinetic parameters of tegavivint.

EXPLORATORY OBJECTIVES:

I. To correlate response to tegavivint with the presence of MYC, FBW7 and SKP2 mutations.

II. To correlate response to tegavivint with TBL1 and c-Myc expression assessed by standard IHC on archived tumor biopsy.

III. To determine the effects of tegavivint on immune cell subsets viability and function.

OUTLINE: This is a dose-escalation study of tegavivint.

Patients receive tegavivint intravenously (IV) on study. Patients also undergo computed tomography (CT) and/or positron emission tomography (PET) and undergo blood sample collection throughout the trial.

Conditions

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Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type Recurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements 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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (Tegavivint)

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.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Tegavivint

Intervention Type DRUG

Given IV

Bone Marrow Biopsy

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Bone Marrow Aspiration

Intervention Type PROCEDURE

Undergo bone marrow biopsy and aspiration

Interventions

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Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Computed Tomography

Undergo CT

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET scan

Intervention Type PROCEDURE

Tegavivint

Given IV

Intervention Type DRUG

Bone Marrow Biopsy

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow biopsy and aspiration

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized Tomography CT CT Scan tomography Medical Imaging, Positron Emission Tomography PET PET Scan Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging PT BC 2059 BC-2059 BC2059 Tegatrabetan Biopsy of bone marrow Biopsy Bone marrow

Eligibility Criteria

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Inclusion Criteria

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)
* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 3 x institutional ULN
* Creatinine clearance \>= 60 ml/min by Cockcroft-Gault (actual body weight will be used to estimate creatinine clearance)
* Patients must be willing and able to understand and give written informed consent and comply with all study related procedures
* Women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use one hormonal contraceptive (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or tubal ligation; and one effective method of contraception, including male condom, female condom, cervical cap, diaphragm or contraceptive sponge or abstain from sex for the duration of study participation and for 4 months following completion of tegavivint administration. 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.

Contraception includes:

* Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
* Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
* Male sterilization (at least 6 months prior to screening). For female patients on the study the vasectomized male partner should be the sole partner for that patient
* Use of oral (estrogen and progesterone), injected or implanted combined hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception
* Sexually active males must use a condom during intercourse while taking drug and for 4 months after stopping study treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential

Exclusion Criteria

* 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
* Neoplasia treated with curative intent, in remission for at least three years and considered at low risk of relapse
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lapo Alinari

OTHER

Sponsor Role lead

Responsible Party

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Lapo Alinari

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Lapo Alinari, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

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Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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The Ohio State Comprehensive Cancer Center

Role: CONTACT

800-293-5066

Facility Contacts

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Lapo Alinari, MD, PhD

Role: primary

614-293-5594

Related Links

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Other Identifiers

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NCI-2023-00200

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-21359

Identifier Type: -

Identifier Source: org_study_id

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