Tegavivint for Large B-Cell Lymphoma

Overseen by Lapo Alinari, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Lapo Alinari

Must not be taking: Antiretrovirals

Disqualifiers: CNS lymphoma, Hepatitis B, Hepatitis C, HIV, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on HIV medications or other drugs that interact with tegavivint, you may not be eligible to participate.

How is the drug Tegavivint different from other treatments for large B-cell lymphoma?

Tegavivint is unique because it targets a specific protein involved in cell signaling pathways, which is different from traditional chemotherapy that targets rapidly dividing cells. This approach may offer a more targeted treatment option with potentially fewer side effects. ^{1 2 3 4 5}

Research Team

Lapo Alinari, MD, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

Adults with relapsed or refractory large B-cell lymphoma who have tried at least two treatments and can't or won't get stem cell transplant or CAR T-cell therapy. They must have measurable disease, adequate organ function, agree to use contraception, and not be pregnant. Excluded are those with certain infections, recent major surgery, other active cancers (with exceptions), uncontrolled illnesses, known allergies to similar drugs, HIV on specific treatments, active CNS lymphoma.

Inclusion Criteria

Patients must be willing and able to understand and give written informed consent and comply with all study related procedures

Platelet count > 75,000/mcL

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x institutional ULN

Exclusion Criteria

I do not have serious heart disease or abnormal heart rhythm issues.

I have an active tuberculosis infection.

I have not had major surgery in the last 3 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive tegavivint intravenously (IV) and undergo CT and/or PET scans and blood sample collection throughout the trial

14 weeks

Multiple visits for IV administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Tegavivint (Beta-catenin Inhibitor)

Trial Overview The trial is testing the safety and optimal dosage of a drug called tegavivint for patients whose large B-cell lymphomas have returned after treatment or haven’t responded to previous therapies. The study involves collecting biospecimens and using imaging tests like CT scans and PET scans to monitor the effects.

Participant Groups

Group I: Treatment (Tegavivint) Experimental Treatment 4 Interventions

Patients receive tegavivint IV on study. Patients also undergo CT and/or PET and undergo blood sample collection throughout the trial.

Who Is Running the Clinical Trial?

Lapo Alinari

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

Recent advancements in therapies for diffuse large B-cell lymphoma (DLBCL) include new agents like polatuzumab combined with bendamustine and rituximab, which are non-cytotoxic and aim to improve patient outcomes.

The approval of CAR-T cell therapies and ongoing development of bispecific antibodies and antibody drug conjugates suggest a promising future for targeted combination therapies in treating B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma: new targets and novel therapies. Cheson, BD., Nowakowski, G., Salles, G.[2022]

In a phase 3 trial involving 879 patients with untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL), the modified regimen pola-R-CHP (which replaces vincristine with polatuzumab vedotin) showed a significantly higher progression-free survival rate at 2 years (76.7%) compared to the standard R-CHOP regimen (70.2%).

The overall survival rates at 2 years were similar between the pola-R-CHP and R-CHOP groups (88.7% vs. 88.6%), indicating that while pola-R-CHP may reduce the risk of disease progression, it does not significantly improve overall survival compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Tilly, H., Morschhauser, F., Sehn, LH., et al.[2022]

Polatuzumab vedotin (PoV) combined with chemotherapy showed a 52.5% overall response rate in 40 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), indicating it is an effective treatment option.

The median overall survival for patients receiving PoV was 8.5 months, but those who underwent subsequent hematopoietic stem cell transplantation had a significantly improved survival of 24 months, highlighting the importance of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin-based salvage immunochemotherapy as third-line or beyond treatment for patients with diffuse large B-cell lymphoma: a real-world experience. Wang, YW., Tsai, XC., Hou, HA., et al.[2022]

In a study of patients with transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of polatuzumab vedotin with bendamustine and rituximab (pola-BR) resulted in a significantly higher complete response (CR) rate of 40% compared to 17.5% with bendamustine and rituximab alone, indicating improved efficacy.

Patients receiving pola-BR also experienced longer progression-free survival (9.5 months vs. 3.7 months) and overall survival (12.4 months vs. 4.7 months), although there were higher rates of certain side effects like neutropenia and peripheral neuropathy, which were mostly manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Sehn, LH., Herrera, AF., Flowers, CR., et al.[2021]

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma: new targets and novel therapies. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin-based salvage immunochemotherapy as third-line or beyond treatment for patients with diffuse large B-cell lymphoma: a real-world experience. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. [2022]