VK-2019 for Lymphoma

Recruiting at 1 trial location

Overseen By Ariel Kobylak

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Thomas Jefferson University

Must not be taking: Herbal preparations, PPIs, OATP1B1/3 drugs

Disqualifiers: Cardiopulmonary diseases, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 28 days per cycle, until progression or toxicity

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically those that inhibit or induce OATP1B1 or OATP1B3, and proton pump inhibitors (PPIs), within 5 half-lives of those agents. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug VK-2019 for treating lymphoma?

The research on similar treatments for extranodal natural killer/T-cell lymphoma (ENKL) shows that asparaginase-based regimens, which are part of the LVDP chemotherapy, have provided encouraging results for relapsed disease and are being investigated for initial treatment. This suggests potential effectiveness for VK-2019 if it shares similar components or mechanisms. ^{1 2 3 4 5}

What is the safety profile of brentuximab vedotin in lymphoma patients?

Brentuximab vedotin has been studied for safety in lymphoma patients, showing that most patients experience some side effects, with common ones being nerve damage, low white blood cell counts, and fever. Some serious side effects, like lung issues, can occur, so close monitoring is recommended, especially for those with existing lung problems. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a Phase Ib in adult patients with relapsed or refractory EBV-positive DLBCL using daily oral dosing of VK-2019 in three dose escalation cohorts: 600 mg/day, 1200 mg/day, 1800 mg/day for 28 days (cycle), until progression or toxicity.

Eligibility Criteria

This trial is for adults with EBV-positive DLBCL, a type of lymphoma, who have tried other treatments that didn't work. Participants will take an oral medication daily in increasing doses to find the right balance between effectiveness and safety.

Inclusion Criteria

4.1 Inclusion Criteria

1. Informed consent obtained prior to any protocol mandated assessment.

3. Patient must have relapsed or refractory EBV-positive DLBCL after a minimum of 2 prior regimens of systemic therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily oral dosing of VK-2019 in three dose escalation cohorts for 28-day cycles

28 days per cycle, until progression or toxicity

Response assessment every 3 cycles

Follow-up

Participants are monitored for survival and safety after treatment

3 years

Treatment Details

Interventions

• VK-2019

Trial Overview VK-2019 is being tested at three different strengths (600 mg, 1200 mg, and 1800 mg) taken once a day for cycles of 28 days. The goal is to see how well it works and what dose is best for people whose lymphoma has come back or hasn't responded to treatment.

Participant Groups

Group I: Treatment (VK-2019 Dose 600mg) Experimental Treatment 1 Intervention

Dose cohort A will dose at 600mg. VK-2019 will be administered daily starting on day 1 of cycle 1 (D1C1). Dose cohort A will dose at 600 mg dose. Treatment cycles will repeat every 28 days , in the absence of disease progression or unacceptable toxicity.

Group II: Treatment (VK-2019 Dose 1800mg) Experimental Treatment 1 Intervention

Dose cohort C will dose at 1800mg. VK-2019 will be administered daily starting on day 1 of cycle 1 (D1C1). Dose cohort C will dose at 1800 mg dose. Treatment cycles will repeat every 28 days , in the absence of disease progression or unacceptable toxicity.

Group III: Treatment (VK-2019 Dose 1200mg) Experimental Treatment 1 Intervention

Dose cohort B will dose at 1200mg.VK-2019 will be administered daily starting on day 1 of cycle 1 (D1C1). Dose cohort B will dose at 1200 mg dose. Treatment cycles will repeat every 28 days , in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

The Wistar Institute

Collaborator

Trials

10

Recruited

790+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 1790 patients with extranodal NK/T-cell lymphoma, achieving progression-free survival at 24 months (PFS24) was associated with significantly better overall survival (OS), with a 5-year OS rate of 92.2% compared to only 19.2% for those who did not achieve PFS24.

The findings suggest that PFS24 can serve as an important early endpoint for evaluating treatment success and risk stratification in ENKTCL, indicating that patients who maintain PFS24 have excellent long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study. Yang, Y., Wang, Y., Liu, X., et al.[2021]

Recent advancements in treating diffuse large B cell lymphoma have led to improved patient outcomes, particularly through dose-dense chemotherapy regimens and the combination of rituximab with chemotherapy, resulting in higher response rates and longer survival.

While low-risk patients have seen significant improvements, high-risk patients still require more effective strategies, potentially through better understanding of genetic factors that contribute to treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies for the treatment of diffuse large B cell lymphoma. Coiffier, B.[2019]

In a review of 2225 lymphoma patients from 4 randomized controlled trials, brentuximab vedotin was found to significantly increase the risk of all-grade adverse events (AEs) and high-grade AEs compared to non-brentuximab vedotin treatments.

Specific AEs associated with brentuximab vedotin included a higher risk of peripheral sensory neuropathy, pyrexia, nausea, vomiting, diarrhea, and alopecia, with particularly high risks for high-grade sensory neuropathy and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. Gao, S., Zhang, M., Wu, K., et al.[2021]

In a study involving 21 patients with relapsed or refractory non-Hodgkin lymphoma, apatinib demonstrated a promising overall response rate of 47.6%, indicating significant antitumor activity.

The treatment was generally well-tolerated, with most adverse events being mild to moderate, including proteinuria and hypertension, suggesting that apatinib could be a safe option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma. Li, L., Xiao, S., Zhang, L., et al.[2022]

In a post-marketing surveillance study of 284 Japanese patients with relapsed/refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, brentuximab vedotin demonstrated an acceptable safety profile, with 74.3% of patients experiencing adverse drug reactions.

Common adverse reactions included peripheral sensory neuropathy and neutropenia, with some patients experiencing severe reactions and a few fatal cases, highlighting the need for careful monitoring, particularly for pulmonary toxicity in at-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of brentuximab vedotin in Japanese patients with relapsed/refractory Hodgkin lymphoma or systemic anaplastic large cell lymphoma: a post-marketing surveillance study. Izutsu, K., Ogura, M., Tobinai, K., et al.[2021]

New-generation Bruton tyrosine kinase inhibitors (BTKi) show a high overall response rate of 92% in treating chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), particularly benefiting younger patients and those receiving combination therapy.

While BTKi-based therapies are generally well-tolerated, they can lead to significant adverse events like cytopenia and hypertension, and zanubrutinib may offer better efficacy than acalabrutinib as a monotherapy for CLL/SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis. Yin, S., Zheng, X., Zhang, W., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study. [2021]

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

Current strategies for the treatment of diffuse large B cell lymphoma. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Beyond first-line non-anthracycline-based chemotherapy for extranodal NK/T-cell lymphoma: clinical outcome and current perspectives on salvage therapy for patients after first relapse and progression of disease. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Risk stratification in extranodal natural killer/T-cell lymphoma. [2010]

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

Trial of LVDP regimen (L-asparaginase, etoposide, dexamethasone, and cisplatin, followed by radiotherapy) as first-line treatment for newly diagnosed, stage III/IV extranodal natural killer/T cell lymphoma. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. [2021]

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

Brentuximab vedotin and AVD followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma. [2021]

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

An open label, single-armed, exploratory study of apatinib (a novel VEGFR-2 tyrosine kinase inhibitor) in patients with relapsed or refractory non-Hodgkin lymphoma. [2022]

9. Japan pubmed.ncbi.nlm.nih.gov

Safety profile of brentuximab vedotin in Japanese patients with relapsed/refractory Hodgkin lymphoma or systemic anaplastic large cell lymphoma: a post-marketing surveillance study. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis. [2023]