Loncastuximab Tesirine + Rituximab for Follicular Lymphoma

Recruiting at 4 trial locations

Overseen By Juan P Alderuccio, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Juan P. Alderuccio, MD

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: CNS involvement, Hepatitis, HIV, 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: 10

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to see if Loncastuximab Tesirine in combination with Rituximab will result in higher complete response rate when given to treat follicular lymphoma.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Loncastuximab Tesirine and Rituximab for treating follicular lymphoma?

Rituximab, one of the drugs in the combination, has been shown to improve outcomes in patients with follicular lymphoma when added to chemotherapy, leading to longer periods without disease progression. It has also been effective as a single treatment in some cases, making it a valuable part of therapy for this type of cancer. ^{1 2 3 4 5}

Is the combination of Loncastuximab Tesirine and Rituximab safe for treating follicular lymphoma?

The safety of Rituximab, a component of the treatment, has been well-studied in various trials for follicular lymphoma and other conditions. It is generally considered safe, with most patients experiencing some treatment-related side effects, but serious adverse events are less common. However, specific safety data for the combination of Loncastuximab Tesirine and Rituximab is not provided in the available research. ^{6 7 8 9 10}

What makes the drug Loncastuximab Tesirine + Rituximab unique for treating follicular lymphoma?

Loncastuximab Tesirine is an antibody-drug conjugate that targets CD19, a protein on B-cells, and delivers a toxic payload directly to cancer cells, while Rituximab targets CD20 on B-cells to help the immune system destroy them. This combination offers a novel approach by using two different mechanisms to attack the cancer cells, potentially improving treatment effectiveness compared to standard therapies that typically use Rituximab with chemotherapy. ^{1 2 11 12 13}

Research Team

Juan P Alderuccio, MD

Principal Investigator

University of Miami

Eligibility Criteria

Adults diagnosed with Follicular Lymphoma who have relapsed or not responded to treatment, and show certain disease characteristics on scans. They must be in relatively good health otherwise, with major organs functioning well and no severe illnesses that could interfere with the study.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I have a confirmed diagnosis of Follicular Lymphoma and if treated before, my cancer still shows CD19.

My blood test shows more than 5,000 lymphoma cells per mm3.

Exclusion Criteria

I have a history of HIV.

I have hepatitis but my PCR test for it is negative.

I do not have severe heart, liver, autoimmune issues, or a recent stroke.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive loncastuximab tesirine on day 1 of each 3-week cycle for 4 cycles and rituximab on days 1, 8, 15 of Cycle 1 and day 1 of Cycle 2

12 weeks

4 visits (in-person) per cycle

Maintenance Phase 1

Participants achieving CR or PR receive loncastuximab tesirine once every 3 weeks and rituximab once during week 7 or 8

8 weeks

3 visits (in-person)

Maintenance Phase 2

Participants achieving CR receive rituximab once during week 7 or 8; those with PR receive loncastuximab tesirine every 3 weeks and rituximab once during week 7 or 8

16 weeks

3 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Loncastuximab tesirine
• Rituximab

Trial Overview The trial is testing whether combining Loncastuximab Tesirine with Rituximab increases the complete response rate in treating Follicular Lymphoma compared to previous treatments patients may have received.

Participant Groups

Group I: Loncastuximab tesirine + Rituximab Experimental Treatment 2 Interventions

During the 12-week Induction Phase (Cycles 1 to 4), participants will receive loncastuximab tesirine on days 1 of each 3-week cycle for Cycles 1 through 4; and rituximab on days 1, 8, 15 of Cycle 1 and day 1 of Cycle 2. Maintenance Phase 1 (Cycle 5) is 8 weeks: Participants achieving complete response (CR) or partial response (PR) during the Induction Phase will receive loncastuximab tesirine once every 3-weeks; and rituximab once during week 7 or 8. Participants achieving a response of Stable Disease (SD) or Progressive Disease (PD) will be taken off treatment. Maintenance Phase 2 (Cycles 6 and 7) is 16 weeks: * Participants achieving CR during Maintenance Phase 1 receive rituximab once during week 7 or 8 of Cycles 6 and 7. * Participants achieving PR during Maintenance Phase 1 receive loncastuximab tesirine once every 3-weeks over each 8 week cycle; and rituximab once during week 7 or 8 of Cycles 6 and 7. * Participants achieving SD or PD will be taken off treatment.

Loncastuximab tesirine is already approved in United States, European Union for the following indications:

Approved in United States as Zynlonta for:

• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low-grade lymphoma, and high-grade B-cell lymphoma

Approved in European Union as Zynlonta for:

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy

Who Is Running the Clinical Trial?

Juan P. Alderuccio, MD

Lead Sponsor

Trials

2

Recruited

120+

ADC Therapeutics S.A.

Industry Sponsor

Trials

32

Recruited

2,700+

Findings from Research

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukaemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials.

The treatment is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for various lymphoma types, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: a review of its use in chronic lymphocytic leukaemia, low-grade or follicular lymphoma and diffuse large B-cell lymphoma. Keating, GM.[2021]

Rituximab significantly improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma when combined with chemotherapy, based on results from multiple randomized trials involving various treatment regimens.

The drug is generally well tolerated, with infusion reactions being the most common side effect, and it is considered cost-effective for treating certain types of lymphoma, reinforcing its status as a standard care option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. Keating, GM.[2017]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

Rituximab, an anti-CD20 antibody, has significantly improved outcomes for patients with follicular lymphoma (FL), achieving long-term remission and prolonged failure-free survival, especially when used as a first-line treatment.

The drug not only works effectively on its own but also enhances the effectiveness of chemotherapy and other targeted therapies, making it a crucial component in the treatment of FL and a benchmark for developing new anti-CD20 monoclonal antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: a benchmark in the development of chemotherapy-free treatment strategies for follicular lymphomas. Karmali, R., Kimby, E., Ghielmini, M., et al.[2020]

A phase 3 trial involving 140 adults with advanced-stage follicular lymphoma showed that the rituximab biosimilar CT-P10 has comparable efficacy to rituximab, with similar progression-free survival rates (61% for CT-P10 vs. 55% for rituximab) after 4 years.

Both CT-P10 and rituximab had similar long-term safety profiles, with 90% of CT-P10 patients and 86% of rituximab patients experiencing treatment-emergent adverse events, indicating that CT-P10 is a safe alternative for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study. Buske, C., Jurczak, W., Sancho, JM., et al.[2021]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

In the phase Ib/II GO29365 study involving 112 patients with relapsed or refractory follicular lymphoma, the combination of polatuzumab vedotin with bendamustine and rituximab (Pola-BR) showed similar PET complete response rates (69.2%) compared to bendamustine and rituximab alone (63.4%).

However, the addition of polatuzumab vedotin was associated with a higher incidence of serious adverse events and cytopenias, indicating that it does not provide a clear benefit over standard treatment regimens for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular lymphoma: a phase Ib/II study. Flowers, CR., Matasar, MJ., Herrera, AF., et al.[2023]

In a study of 145 patients with chronic lymphoid leukemia (CLL) and indolent non-Hodgkin lymphoma treated with bendamustine and rituximab, 25% experienced late onset neutropenia (LON), indicating a significant risk associated with this treatment.

The incidence of LON was particularly high in patients with follicular lymphoma, leading to treatment discontinuation in many cases, highlighting the need for close monitoring and prophylactic measures during and after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Description of late onset neutropenia in indolent lymphoma patients treated with bendamustine plus rituximab. Verriere, B., Gastaud, L., Chamorey, E., et al.[2018]

A meta-analysis of four clinical trials involving 1223 patients found no significant differences in efficacy between rituximab biosimilars and the original drug MabThera for treating low-tumour-burden follicular lymphoma, indicating that biosimilars are just as effective.

Safety profiles were also comparable, with no significant differences in serious adverse events or infusion-related reactions between the biosimilars and MabThera, supporting the use of biosimilars as a safe alternative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab biosimilars or reference product as first-line treatment in patients with low-tumour-burden follicular lymphoma: A systematic review and meta-analysis. Yang, L., Zheng, Z., Li, N., et al.[2022]

Rituximab, a monoclonal antibody targeting CD20 on B lymphocytes, significantly prolongs progression-free survival in patients with follicular lymphoma when used as a two-year maintenance therapy after initial treatment, compared to observation.

The maintenance therapy with rituximab also delays the need for subsequent lymphoma treatments and has an acceptable safety profile, showing no new or unexpected adverse events compared to the initial induction therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: as first-line maintenance therapy following rituximab-containing therapy for follicular lymphoma. Croxtall, JD.[2021]

In a phase II trial involving 29 patients with untreated follicular lymphoma, rituximab combined with fludarabine and mitoxantrone achieved a high overall response rate of 100% and a complete remission rate of 66%, with notably higher remission rates in female patients.

Pharmacokinetic analysis revealed significant variability in rituximab serum concentrations, which correlated with treatment outcomes; specifically, higher serum levels were linked to better remission quality and longer progression-free survival, suggesting that dosing may need to be tailored based on patient characteristics like gender and bone marrow infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Jäger, U., Fridrik, M., Zeitlinger, M., et al.[2021]

Rituximab was the first monoclonal antibody approved for cancer therapy and has significantly improved survival rates in patients with diffuse large cell lymphoma when combined with CHOP chemotherapy.

Initially approved in 1997 for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma, rituximab is also being researched for other B-cell malignancies and nonmalignant diseases like autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. King, KM., Younes, A.[2015]

References

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

Rituximab: a review of its use in chronic lymphocytic leukaemia, low-grade or follicular lymphoma and diffuse large B-cell lymphoma. [2021]

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

Spotlight on rituximab in chronic lymphocytic leukemia, low-grade or follicular lymphoma, and diffuse large B-cell lymphoma. [2017]

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

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. [2021]

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

Rituximab: clinical development and future directions. [2019]

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

Rituximab: a benchmark in the development of chemotherapy-free treatment strategies for follicular lymphomas. [2020]

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

Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study. [2021]

7. England pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular lymphoma: a phase Ib/II study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Description of late onset neutropenia in indolent lymphoma patients treated with bendamustine plus rituximab. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of rituximab biosimilars or reference product as first-line treatment in patients with low-tumour-burden follicular lymphoma: A systematic review and meta-analysis. [2022]

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

Rituximab: as first-line maintenance therapy following rituximab-containing therapy for follicular lymphoma. [2021]

12. Italy pubmed.ncbi.nlm.nih.gov

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. [2015]