Loncastuximab + Rituximab for Large B-Cell Lymphoma

(CORAL Trial)

Overseen By Catherine Cromar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Anti-CD19 therapy

Disqualifiers: Chronic liver disease, Autoimmune disease, CNS involvement, 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: Unknown

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of combining two treatments, Loncastuximab tesirine (an antibody-drug conjugate) and Rituximab, for large B-cell lymphoma that has returned or isn't responding to previous treatments. Specifically, the trial tests these treatments before patients receive CAR-T cell therapy. This trial may suit individuals with large B-cell lymphoma that has recurred or resisted past treatments and who need additional therapy before starting CAR-T cell therapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering early access to potentially effective therapies.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions a washout period (time without taking certain medications) for prohibited medications before starting treatment. 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?

Research has shown that combining Loncastuximab tesirine with Rituximab has been tested in people with certain types of lymphoma. One study administered this combination to patients who did not respond to other treatments. The study found that the treatment was generally well-tolerated, although some side effects occurred. Common side effects included low blood cell counts, tiredness, and skin rashes.

Another study focused on patients with relapsed or hard-to-treat large B-cell lymphoma. It showed similar results, with the treatment being mostly well-tolerated. Patients experienced some side effects, such as low blood cell counts and tiredness, but these were manageable.

These findings suggest that the combination of Loncastuximab tesirine and Rituximab is considered safe enough for further study. However, individual reactions can vary. Participants in any clinical trial should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Loncastuximab tesirine is unique because it combines an antibody-drug conjugate that specifically targets CD19, a protein found on the surface of B-cell lymphoma cells, with a powerful chemotherapy agent. This targeted approach allows the treatment to deliver the chemotherapy directly to the cancer cells, potentially minimizing damage to healthy cells. Researchers are excited about this treatment because it offers a novel way to enhance the effectiveness of existing therapies like Rituximab and could improve outcomes for patients who undergo subsequent CAR-T cell therapy. This approach could represent a significant advancement over standard chemotherapy and immunotherapy combinations currently available for large B-cell lymphoma.

What evidence suggests that Loncastuximab tesirine and Rituximab might be an effective treatment for large B-cell lymphoma?

Studies have shown promising results for Loncastuximab tesirine in treating difficult cases of large B-cell lymphoma that have returned or not responded to previous treatments. In one study, 95% of patients remained alive after 12 months of treatment. Another study found it effective for patients who had already tried CAR-T therapy. Additionally, when combined with other treatments like glofitamab, Loncastuximab tesirine achieved a 93.3% success rate in reducing cancer, demonstrating its potential to significantly help patients. In this trial, all participants will receive a combination of Loncastuximab tesirine and Rituximab before standard of care CAR-T cell therapy. These findings suggest Loncastuximab tesirine could be a powerful option for those with challenging cases of large B-cell lymphoma. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for individuals with relapsed or refractory large B-cell lymphoma who are candidates for CAR-T therapy. Specific eligibility criteria details were not provided, so interested participants should inquire further to determine if they qualify.

Inclusion Criteria

My doctor says I need temporary treatment before my main therapy.

Adequate organ function as defined as: Hematologic: Absolute neutrophil count (ANC) ≥ 1000/mm3, Platelet count ≥ 75,000/mm3, Hemoglobin ≥ 8 g/dL; Hepatic: Bilirubin ≤1.5 x upper limit of normal (ULN) or ≤3 x ULN with document liver involvement and/ or Gilbert's disease, Transaminases (AST or ALT) ≤ 3 x ULN or ≤ 5 x ULN with documented liver involvement; Renal: Estimated creatinine clearance ≥ 60 mL/min by Cockcroft-Gault formula

Subjects or their legal representatives must be able to read, understand, and provide informed consent to participate in the trial

Exclusion Criteria

I have a lymphatic system disorder after receiving a transplant.

Active autoimmune disease which, in the opinion of the investigator, may negatively impact subject safety or interfere with study participation

My liver disease is severe (Child-Pugh class C).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bridging Therapy

Participants receive Loncastuximab tesirine and Rituximab as bridging therapy before CAR-T cell therapy

1 month

Multiple visits for administration and monitoring

CAR-T Cell Therapy

Participants undergo standard-of-care CD19 CAR T-cell therapy

1 month

Inpatient stay for CAR-T administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after CAR-T cell therapy

3 months

Regular follow-up visits for assessment

Long-term Follow-up

Participants are monitored for long-term safety and efficacy outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Loncastuximab Tesirine

Trial Overview The study is testing the safety and efficiency of Loncastuximab Tesirine and Rituximab as a bridging therapy before patients receive standard-of-care CD19 CAR T-cell therapy.

How Is the Trial Designed?

Group I: Treatment: All Patients Experimental Treatment 2 Interventions

The study will investigate the effectiveness of Loncastuximab tesirine and Rituximab (Lonca-R) prior to standard of care CAR-T cell therapy.

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

ADC Therapeutics S.A.

Industry Sponsor

Trials

32

Recruited

2,700+

Published Research Related to This Trial

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]

Loncastuximab tesirine is an antibody-drug conjugate that targets B cell lymphomas, specifically approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL) after two or more lines of treatment.

The drug works by using an anti-CD19 antibody to deliver a DNA-alkylating agent directly to B cells, enhancing its efficacy in targeting cancer cells while minimizing damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. Lee, A.[2021]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody drug, has been safely administered at full doses to patients with relapsed/refractory DLBCL despite their severe hepatic dysfunction, suggesting potential efficacy in this challenging patient population.

The cases presented highlight the need for further investigation into the safety and dosing guidelines of loncastuximab tesirine-lpyl in patients with moderate to severe liver impairment, as current guidance from the manufacturer is unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of loncastuximab tesirine-lpyl in diffuse large B-cell lymphoma with severe hepatic dysfunction. Baek, GT., Huang, IJ., Gopal, AK.[2023]

The review analyzed 56 studies on anti-CD20 monoclonal antibodies combined with chemotherapy for treating relapsed or refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL), highlighting a significant focus on rituximab due to the larger amount of available data.

Despite the promising potential of these combination regimens, the evidence remains inconclusive regarding the efficacy differences among the anti-CD20 agents, underscoring the need for more direct comparative studies to guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Evidence-based Review of Anti-CD20 Antibody-containing Regimens for the Treatment of Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Diffuse Large B-cell Lymphoma, or Follicular Lymphoma. Falchi, L., Ferrajoli, A., Jacobs, I., et al.[2019]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.3% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma during the phase II LOTIS-2 trial, indicating its efficacy as a treatment option.

The drug demonstrated a tolerable safety profile with common side effects including neutropenia and thrombocytopenia, and no new safety concerns were identified in the phase II trial, suggesting it is safe for further testing in various non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. Zurko, J., Hamadani, M.[2021]

Rituximab, an anti-CD20 monoclonal antibody, demonstrated a 43% overall response rate in a phase II trial involving 31 patients with bulky relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma, indicating its efficacy as a treatment option.

The treatment was well-tolerated, with no patients discontinuing due to adverse events, and it showed a median time to progression of 8.1 months, highlighting its safety and potential for managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. Davis, TA., White, CA., Grillo-López, AJ., et al.[2022]

Rituximab has been shown to significantly improve progression-free and overall survival in patients with various types of non-Hodgkin lymphoma and chronic lymphocytic leukaemia (CLL), based on a systematic review of 56 randomized controlled trials.

The consensus guidelines recommend rituximab for use in combination with chemotherapy for initial treatment of aggressive B-cell lymphomas, maintenance therapy for indolent B-cell lymphomas, and as part of treatment regimens for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in Lymphoma and Chronic Lymphocytic Leukaemia: A Practice Guideline. Prica, A., Baldassarre, F., Hicks, LK., et al.[2018]

Recent advances in targeted therapies for non-Hodgkin lymphoma, particularly the anti-CD20 monoclonal antibody rituximab, are expected to significantly improve patient care by inhibiting specific disease pathways.

Combining rituximab with other agents, such as monoclonal antibodies, immunomodulatory drugs, and Bcl-2 inhibitors, shows promise for enhancing treatment efficacy, especially in patients who do not respond to rituximab alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapies for non-Hodgkin lymphoma: rationally designed combinations. Martin, P., Leonard, JP.[2019]

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]

Alemtuzumab has proven effective in treating chronic lymphocytic leukemia, both as a standalone treatment and in combination with other therapies like fludarabine or rituximab, showing improved response rates and survival compared to traditional chemotherapy.

Despite its efficacy, there are safety concerns due to known toxicities associated with alemtuzumab, particularly when used in combination therapies, which require careful management to avoid adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab: what is the secret to safe therapy? Elter, T., Hallek, M., Montillo, M.[2017]

Rituximab has significantly improved survival rates in patients with non-Hodgkin lymphomas, but there is a lack of comprehensive data on its long-term safety, indicating a need for extended patient follow-up.

Current literature provides limited guidance on systematic follow-up models for patients receiving rituximab, highlighting the necessity for developing monitoring strategies to ensure patient safety and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? Hegele, V., Stoll, P., Wüst, D., et al.[2021]

Citations

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

Outcomes with loncastuximab tesirine following CAR T ... OS at 12 months was 95%. In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723022285

482 Real-World Clinical Effectiveness of Loncastuximab ... In this real-world study, we examined the effectiveness of lonca for pts with R/R DLBCL following CAR-T. This is the first study to examine lonca at 3L ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39540227/

Loncastuximab in high-risk and heavily pretreated relapsed ... The median event-free survival and overall survival were 2.1 and 4.6 months, respectively. Those with bulky disease and high-grade B-cell ...

4. haematologica.org haematologica.org/article/view/11820

Loncastuximab in high-risk and heavily pretreated ... Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an ...

5. onclive.com onclive.com/view/loncastuximab-tesirine-plus-glofitamab-shows-early-safety-and-efficacy-in-r-r-dlbcl

Loncastuximab Tesirine Plus Glofitamab Shows Early ... Loncastuximab tesirine and glofitamab combination showed a 93.3% overall response rate in relapsed/refractory DLBCL patients, with an 86.7% ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05144009

NCT05144009 | A Study of Loncastuximab Tesirine and ... The main objective of the trial is to assess the efficacy and tolerability of Lonca-R in unfit and frail participants with previously untreated DLBCL. Detailed ...

7. 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 ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025022967

ABCL-758: Updated Safety Run-In Results From LOTIS-5: ... Safety run-in included 20 patients (18 DLBCL/2 HGBL), median age: 74.5 years, median 1 prior therapy (4 refractory to last line). As of October 4, 2024, ...

9. 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 ...

10. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00345-4/abstract

Loncastuximab tesirine with rituximab in patients ... Loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma: long-term efficacy and safety from the phase II LOTIS-2 study.