Loncastuximab Tesirine + Rituximab for Diffuse Large B-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Joseph M Tuscano

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph Tuscano

Must not be taking: Immunosuppressives, CAM, others

Disqualifiers: CNS involvement, Severe infections, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medicines to treat diffuse large B-cell lymphoma, a type of blood cancer. It combines targeted therapies, such as loncastuximab tesirine (Zynlonta) and rituximab, with chemotherapy drugs to determine if they work better together against this high-risk cancer. Individuals who have not yet received treatment for this type of lymphoma and have specific markers on their cancer cells might be suitable candidates. The trial aims to assess whether this new combination is more effective than standard treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you must stop all current medications. However, you cannot use certain treatments like complementary and alternative medications within 1 week, investigational agents within 3 weeks, or immunosuppressive medications within 14 days before starting the trial. Some exceptions apply, such as steroids and bisphosphonate therapy. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study showed that patients who received the combination of loncastuximab tesirine and rituximab generally tolerated the treatment well. Common side effects included low blood cell counts and fatigue, but these were manageable. Research has also shown that rituximab alone is usually well-tolerated, with mostly mild side effects like fever or chills.

The chemotherapy drugs used in this trial—doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone—are effective but can cause side effects such as nausea, hair loss, or a higher risk of infection. These side effects are well-known, and healthcare teams are skilled in managing them.

While this trial focuses on the treatment's effectiveness, earlier studies provide reassurance about the safety of these drugs when used together. Participants should discuss any concerns with the trial team to understand how they will monitor and manage side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Loncastuximab Tesirine and Rituximab for treating Diffuse Large B-Cell Lymphoma because it offers a novel mechanism of action compared to existing treatments. Unlike standard therapies that primarily target cancer cells with chemotherapy, Loncastuximab Tesirine is an antibody-drug conjugate that precisely delivers a cytotoxic agent directly to the cancer cells, potentially reducing damage to healthy cells. This targeted approach not only promises improved efficacy but also minimizes side effects, which can significantly enhance patients' quality of life. Additionally, combining it with Rituximab, a monoclonal antibody that further targets and marks cancer cells for destruction, could offer a more powerful and comprehensive attack on the lymphoma.

What evidence suggests that this trial's treatments could be effective for diffuse large B-cell lymphoma?

Research has shown that loncastuximab tesirine effectively treats diffuse large B-cell lymphoma (DLBCL), particularly in challenging cases where other treatments have failed. It targets cancer cells by attaching to CD19 receptors and delivering a drug to kill them. In this trial, participants will receive a combination of loncastuximab tesirine and rituximab. Rituximab attaches to CD20 receptors on cancer cells, helping the immune system attack them. Studies indicate that using these treatments together can yield positive results in patients with recurrent or hard-to-treat DLBCL. This combination therapy shows promise for those with high-risk forms of the disease. ^{1 4 6 7 8}

Who Is on the Research Team?

Joseph M. Tuscano

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for adults with untreated high-risk diffuse large B-cell lymphoma, confirmed by specific criteria. Participants must have measurable disease, be in relatively good health (ECOG <=2), and have a life expectancy of at least 6 months. They should not have had certain previous treatments or conditions that could affect the study results.

Inclusion Criteria

Leukocytes >= 2,500/uL

My kidneys are functioning well enough to clear creatinine.

Life expectancy >= 6 months

Exclusion Criteria

I have a skin condition like eczema, psoriasis, or vitiligo.

Specific timeframes for prior treatments

I have a serious liver condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive rituximab, loncastuximab tesirine, etoposide, doxorubicin, vincristine, prednisone, and cyclophosphamide

6 weeks

Multiple visits (in-person) for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Regular visits (in-person) for CT or PET/CT scans

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Etoposide
• Loncastuximab Tesirine
• Prednisone
• Rituximab
• Vincristine

Trial Overview The trial tests loncastuximab tesirine and rituximab followed by DA-EPOCH-R chemotherapy to see if it's more effective for treating high-risk diffuse large B-cell lymphoma than standard therapies. It combines targeted therapy with traditional chemotherapy.

How Is the Trial Designed?

Group I: Treatment (Lonca-R, DA-EPOCH-R) Experimental Treatment 7 Interventions

Patients receive rituximab IV, loncastuximab tesirine IV, etoposide IV, doxorubicin IV, vincristine IV, prednisone PO, and cyclophosphamide IV on study. Patients also undergo collection of blood samples and bone marrow aspiration and biopsy at screening and CT or PET/CT at screening, throughout the study, and during follow up.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Joseph Tuscano

Lead Sponsor

Trials

8

Recruited

180+

ADC Therapeutics

Collaborator

Trials

2

Recruited

20+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

ADC Therapeutics S.A.

Industry Sponsor

Trials

32

Recruited

2,700+

Published Research Related to This Trial

In a study of 304 Chinese breast cancer patients undergoing doxorubicin-cyclophosphamide chemotherapy, adding olanzapine to an aprepitant-based antiemetic regimen significantly improved the complete response rate and quality of life compared to a standard doublet regimen.

The netupitant/palonosetron/dexamethasone combination was found to be more effective than the aprepitant/ondansetron/dexamethasone regimen, indicating that the choice of antiemetic can greatly impact patient outcomes during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of optimal contemporary antiemetic prophylaxis for doxorubicin-cyclophosphamide chemotherapy in Chinese cancer patients: post-hoc analysis of 3 prospective studies. Yeo, W., Li, L., Lau, TK., et al.[2021]

In a study of 134 patients with diffuse large B-cell lymphoma (DLBCL) involving the testis, the addition of rituximab to standard chemotherapy (R-CHOP) significantly improved progression-free survival and overall survival, with hazard ratios of 0.42 and 0.39 respectively, indicating a strong protective effect.

Despite the benefits of rituximab in reducing lymphoma recurrence, the risk of central nervous system (CNS) relapse remained high, suggesting that additional strategies for CNS prophylaxis are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era. Kridel, R., Telio, D., Villa, D., et al.[2017]

In a phase 2 trial involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), loncastuximab tesirine demonstrated a significant overall response rate of 48.3%, indicating its effectiveness as a treatment option for this challenging patient population.

The treatment was associated with an acceptable safety profile, with serious adverse events occurring in 39% of patients, but none were directly linked to loncastuximab tesirine, suggesting it may be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Caimi, PF., Ai, W., Alderuccio, JP., et al.[2021]

In a study of 112 patients under 65 years old with diffuse large B-cell lymphoma, the combination of rituximab and high-dose sequential chemotherapy led to an impressive 80% clinical remission rate, demonstrating its efficacy in treating this aggressive cancer.

At a median follow-up of 48 months, 78% of patients remained alive and 73% were in continuous remission, indicating that this treatment significantly improves life expectancy compared to conventional chemotherapy for younger patients with higher risk scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Tarella, C., Zanni, M., Di Nicola, M., et al.[2022]

An integrated pharmacokinetic model for loncastuximab tesirine in treating relapsed/refractory B cell non-Hodgkin lymphoma showed that the drug's exposure is significantly associated with better overall response rates and overall survival, based on data from 328 patients.

Factors like low albumin levels and mild to moderate liver impairment were linked to reduced drug exposure and poorer outcomes, but the study suggests maintaining the current dosing schedule without increases, despite these challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety Exposure-Response Analysis of Loncastuximab Tesirine in Patients with B cell non-Hodgkin Lymphoma. Hess, B., Townsend, W., Ai, W., et al.[2022]

A pilot study involving 80 patients with diffuse large B-cell lymphoma (DLBCL) showed that administering rituximab with chemotherapy every 14 days (R-CHOP-14) is feasible and effective, with 73% of patients achieving complete remission after treatment.

With a median follow-up of 26 months, the study reported a progression-free survival rate of 72% and an overall survival rate of 86% at 30 months, indicating promising long-term outcomes for patients under 70 years old.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

R-CHOP-14 in patients with diffuse large B-cell lymphoma younger than 70 years: a multicentre, prospective study. Rueda, A., Sabin, P., Rifá, J., et al.[2015]

In a study of 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

In a study involving 197 patients undergoing high-dose chemotherapy, dolasetron and ondansetron were found to be equally effective in preventing nausea and vomiting, with total response rates of 45.7% for dolasetron and 46.9% for ondansetron.

Both dolasetron and ondansetron were well-tolerated by patients, indicating that they are safe options for managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, multicenter, open-label comparison of the antiemetic efficacy of dolasetron versus ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy. Mandanas, RA., Beveridge, R., Rifkin, RM., et al.[2020]

A systematic review of 299 studies involving 58,412 patients found that 5-HT3 receptor antagonists are generally safe and effective for reducing nausea and vomiting in chemotherapy patients, with no significant differences in cardiac risks among the agents compared.

However, dolasetron combined with dexamethasone was associated with a higher risk of QTc prolongation compared to ondansetron combined with dexamethasone, indicating a potential safety concern with this combination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis. Tricco, AC., Blondal, E., Veroniki, AA., et al.[2022]

In a phase II study involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma, loncastuximab tesirine demonstrated significant improvements in health-related quality of life, with a notable increase in overall health scores over treatment cycles.

The treatment was well-tolerated, with over 60% of patients reporting minimal bother from side effects, indicating a favorable safety profile alongside its antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life, Symptoms, and Tolerability of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Spira, A., Zhou, X., Chen, L., et al.[2022]

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

In a study involving 307 cancer patients, dolasetron mesylate effectively prevented nausea and vomiting during chemotherapy, with a significant increase in complete response rates from 44.7% at 25 mg to 82.5% at 200 mg.

All doses of dolasetron were well tolerated, with the most common side effects being headache and dizziness, indicating a favorable safety profile for this antiemetic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy. Oral Dolasetron Dose Response Study Group. Grote, TH., Pineda, LF., Figlin, RA., et al.[2013]

In a pilot study involving 69 cancer patients, intravenous dolasetron was found to be safe and effective in preventing nausea and vomiting caused by doxorubicin and/or cyclophosphamide, with 61% of patients achieving complete control of emesis.

The study indicated that while increasing doses of dolasetron did not significantly improve antiemetic efficacy, factors like age, gender, and type of chemotherapy were important predictors of treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-ranging evaluation of the antiemetic efficacy of intravenous dolasetron in patients receiving chemotherapy with doxorubicin or cyclophosphamide. Hesketh, PJ., Gandara, DR., Hesketh, AM., et al.[2019]

In a study involving 80 patients from the LOTIS-2 trial, loncastuximab tesirine (Lonca) demonstrated a significantly higher overall response rate (53.4%) compared to chemoimmunotherapy (CIT) treatments (40.3%) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

Lonca also showed improved overall survival, with a median survival of 10.8 months compared to 6.4 months for CIT, indicating it may be a more effective treatment option for patients with R/R DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Hamadani, M., Chen, L., Song, Y., et al.[2022]

In a phase 1 study involving 183 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 45.6%, with 26.7% achieving complete responses, indicating its potential as an effective treatment option.

The study established a recommended dose of 150 µg/kg for phase 2 trials, with an acceptable safety profile characterized by manageable hematologic toxicities, suggesting that loncastuximab tesirine could be a viable alternative to current therapies for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Hamadani, M., Radford, J., Carlo-Stella, C., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05144009

NCT05144009 | A Study of Loncastuximab Tesirine and ... A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/​Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL) (LOTIS-9).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11276998/

Loncastuximab Tesirine in the Treatment of Relapsed or ... Several studies have proven its efficacy in the treatment of refractory cases of DLBCL with a good safety profile, with the main adverse effects being ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS7097

LOTIS-5: An ongoing, phase 3, randomized study of ... Background: Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) typically have poor outcomes following standard ...

4. nature.com nature.com/articles/s41408-024-01195-4

Outcomes with loncastuximab tesirine following CAR T-cell ... In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings including those who were resistant to or ...

5. zynlonta.com zynlonta.com/study-results/

Study Results | ZYNLONTA® (loncastuximab tesirine-lpyl ... ZYNLONTA® was effective for many people who had past R/R DLBCL therapies. The ZYNLONTA® clinical trial included people who had already received a variety of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9431578/

PHASE 3 RANDOMIZED STUDY OF LONCASTUXIMAB ... Background: Patients (pts) with refractory or relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) have poor outcomes with standard treatment. Loncastuximab ...

7. ir.adctherapeutics.com ir.adctherapeutics.com/press-releases/press-release-details/2025/ADC-Therapeutics-Announces-Presentation-of-LOTIS-7-Clinical-Trial-Data-at-the-European-Hematology-Association-2025-Congress-EHA2025-and-the-18th-International-Conference-on-Malignant-Lymphoma-ICML/default.aspx

ADC Therapeutics Announces Presentation of LOTIS-7 ... ZYNLONTA® plus glofitamab (COLUMVI®) demonstrated ORR of 95.5% and CR of 90.9%, among 22 evaluable patients with relapsed/refractory DLBCL.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023013320

ABCL-515 Updated Results of the Safety Run-In ... Part 1 enrolled 20 patients in a nonrandomized safety run-in; part 2 will randomly assign approximately 330 patients to receive Lonca-R or rituximab-gemcitabine ...