Loncastuximab + Rituximab for Large B-Cell Lymphoma

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

Trial Summary

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.

What data supports the effectiveness of the drug Loncastuximab Tesirine when combined with Rituximab for treating Large B-Cell Lymphoma?

Rituximab, when used with chemotherapy, has shown benefits in treating B-cell lymphomas, including improved survival rates. Although specific data on Loncastuximab Tesirine is not provided, the combination with Rituximab may enhance treatment effectiveness based on Rituximab's proven success in similar conditions. ^{1 2 3 4 5}

Is the combination of Loncastuximab and Rituximab safe for treating large B-cell lymphoma?

Rituximab has been shown to have a favorable safety profile, with most side effects being mild to moderate and decreasing with continued use. While specific safety data for Loncastuximab Tesirine in combination with Rituximab is not provided, Rituximab alone is generally well-tolerated in humans. ^{6 7 8 9 10}

What makes the drug Loncastuximab Tesirine unique for treating large B-cell lymphoma?

Loncastuximab Tesirine is unique because it is an antibody-drug conjugate that specifically targets CD19 on B cells, delivering a potent toxin directly to the cancer cells. This targeted approach can be more effective and potentially have fewer side effects compared to traditional chemotherapy, especially for patients with relapsed or refractory large B-cell lymphoma. ^{11 12 13 14 15}

What is the purpose of this trial?

The purpose of this clinical trial is to learn if the study treatment Loncastuximab tesirine and Rituximab is safe and efficient before standard of care chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed or refractory large B-cell lymphoma.

Eligibility Criteria

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.

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

I am willing and able to follow the study's requirements.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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 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]

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]

References

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

Improving therapeutic activity of anti-CD20 antibody therapy through immunomodulation in lymphoid malignancies. [2019]

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

The future of CD20 monoclonal antibody therapy in B-cell malignancies. [2019]

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

Rituximab in Lymphoma and Chronic Lymphocytic Leukaemia: A Practice Guideline. [2018]

4. United States 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. [2019]

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

Targeted therapies for non-Hodgkin lymphoma: rationally designed combinations. [2019]

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

Single-agent monoclonal antibody efficacy in bulky non-Hodgkin's lymphoma: results of a phase II trial of rituximab. [2022]

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

Phase 1/2 study of ocaratuzumab, an Fc-engineered humanized anti-CD20 monoclonal antibody, in low-affinity FcγRIIIa patients with previously treated follicular lymphoma. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Rituximab: the first monoclonal antibody approved for the treatment of lymphoma. [2019]

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

Alemtuzumab: what is the secret to safe therapy? [2017]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? [2021]

11. England 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. [2021]

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

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. [2022]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. [2021]

14. Spain pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. [2021]

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

Safety of loncastuximab tesirine-lpyl in diffuse large B-cell lymphoma with severe hepatic dysfunction. [2023]