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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new combination of medications, Loncastuximab Tesirine (an antibody-drug conjugate) and Rituximab (a monoclonal antibody), can improve treatment outcomes for people with follicular lymphoma, a type of blood cancer. The goal is to determine if this combination can help more patients fully respond to treatment compared to current options. The trial seeks participants with follicular lymphoma that has returned or not responded to previous treatments and who have specific symptoms like large lymph nodes or significant weight loss. Participants will receive these medications in cycles, and their response will guide their treatment path. Those who have had at least one previous treatment for follicular lymphoma and experience frequent recurrences may find this trial suitable. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that using loncastuximab tesirine with rituximab for follicular lymphoma is generally safe. Studies have found that this combination has significant positive effects and a manageable safety profile. While some side effects may occur, they are usually not serious and can be treated with standard care. Previous patients who received this combination handled it well, which is encouraging for its safety in humans. ^{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 follicular lymphoma because it offers a unique approach compared to standard treatments like chemoimmunotherapy. Loncastuximab tesirine is an antibody-drug conjugate, which means it specifically targets cancer cells and delivers a potent anti-cancer drug directly to them, minimizing damage to healthy cells. This targeted mechanism could lead to better outcomes with fewer side effects. Additionally, the combination with rituximab, a monoclonal antibody that also targets cancer cells, may enhance the overall effectiveness of treatment. This innovative approach holds promise for more precise and effective management of follicular lymphoma.

What evidence suggests that Loncastuximab Tesirine + Rituximab might be an effective treatment for follicular lymphoma?

This trial will evaluate the combination of loncastuximab tesirine and rituximab for treating follicular lymphoma, a type of blood cancer. Research has shown that this combination may be effective, with 35% of patients in previous studies achieving a complete response, meaning their cancer was no longer visible on scans. Specifically, this treatment also proved effective for patients whose cancer was difficult to treat or had returned, with many experiencing no worsening of their cancer for at least 12 months. The combination demonstrated effectiveness and manageable side effects, suggesting it could be a helpful option for people with follicular lymphoma. ^{2 4 5 6 7}

Who Is on the Research Team?

Juan P Alderuccio, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

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

Loncastuximab tesirine with rituximab in patients ... In this study, we evaluated loncastuximab tesirine combined with rituximab for second-line and later treatment of follicular lymphoma.

2. ir.adctherapeutics.com ir.adctherapeutics.com/press-releases/press-release-details/2024/ADC-Therapeutics-Announces-The-Lancet-Haematology-Publication-of-Data-from-Investigator-Initiated-Trial-Evaluating-ZYNLONTA-in-Combination-with-Rituximab-to-Treat-RelapsedRefractory-Follicular-Lymphoma/

Press Release Details The publication titled, "Loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: a single centre, ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302624003454

Articles Loncastuximab tesirine with rituximab in patients ... The complete response rate assessed by CT in follicular lymphoma was 35% (n=51 of 147). Emerging therapies aiming to improve outcomes in patients with relapsed ...

4. ashpublications.org ashpublications.org/ashclinicalnews/news/7624/Loncastuximab-With-Rituximab-Effective-in-High

Loncastuximab With Rituximab Effective in High-Risk R/R ... Loncastuximab tesirine with rituximab was effective and had an acceptable side effect profile in the treatment of high-risk relapsed or refractory (R/R) ...

5. onclive.com onclive.com/view/dr-alderuccio-on-loncastuximab-tesirine-with-rituximab-in-r-r-follicular-lymphoma

Dr Alderuccio on Loncastuximab Tesirine With Rituximab ... At the current follow-up, CRs appeared durable, with a 12-month progression-free survival (PFS) rate of 94.6% (95% CI, 79.9%-98.6%). The median ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39662486/

Loncastuximab tesirine with rituximab in patients ... Interpretation: Loncastuximab tesirine with rituximab showed clinically meaningful activity in relapsed or refractory follicular lymphoma, and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04998669

Study Details | NCT04998669 | Loncastuximab Tesirine in ... 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 ...