Brentuximab + Bendamustine for Follicular Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph Tuscano

Must not be taking: Immunosuppressants, Antibiotics, 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: 19

Duration: 18 weeks

23 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial investigates how well brentuximab vedotin and bendamustine work in treating patients with follicular lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as bendamustine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to determine if the combination of brentuximab vedotin plus bendamustine is safe and to determine the effectiveness of the combination.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like chemotherapy or radiotherapy must be stopped at least 2 weeks before starting the trial, and herbal therapies require a 1-week washout period (time without taking them). Please consult with the trial team for guidance on your specific medications.

What data supports the effectiveness of the drug combination Brentuximab and Bendamustine for treating follicular lymphoma?

Bendamustine, when combined with rituximab, has shown high effectiveness in treating indolent lymphomas, including follicular lymphoma, with good response rates and the ability to eradicate minimal residual disease. This suggests that Bendamustine is effective in similar lymphoma treatments, which may support its use in combination with Brentuximab for follicular lymphoma. ^{1 2 3 4 5}

Is the combination of Brentuximab and Bendamustine safe for humans?

Bendamustine has been studied in patients with non-Hodgkin lymphoma, and it was generally well-tolerated with no significant increase in adverse events when used with anti-nausea medications. However, specific safety data for the combination of Brentuximab and Bendamustine in humans is not provided in the available research. ^{6 7 8 9 10}

How does the drug combination of Brentuximab Vedotin and Bendamustine differ from other treatments for follicular lymphoma?

The combination of Brentuximab Vedotin and Bendamustine is unique because it targets follicular lymphoma by combining a targeted therapy (Brentuximab Vedotin) with a chemotherapy agent (Bendamustine), potentially offering a novel approach for patients who have not responded to other treatments. This combination has shown promise in treating other types of lymphoma, such as Hodgkin lymphoma, suggesting it may offer benefits for follicular lymphoma as well. ^{2 4 11 12 13}

Research Team

Joseph M. Tuscano

Principal Investigator

University of California, Davis

Eligibility Criteria

This trial is for adults with relapsed or refractory follicular lymphoma, a type of non-Hodgkin lymphoma. Participants must have had at least one prior treatment, measurable disease via scans, and be generally healthy with proper organ function. They should not be pregnant and agree to use contraception. Those with recent infections, certain allergies, severe liver disease, uncontrolled illnesses or who've recently used similar drugs are excluded.

Inclusion Criteria

Hemoglobin >= 8 g/dL

Absolute neutrophil count >= 1,000/mcL

Platelets >= 50,000/mcL

Exclusion Criteria

You have a known allergy or sensitivity to products made from Chinese hamster ovary cells or other human antibodies made in a laboratory.

I have not had signs of infection in the last 2 weeks.

I have taken a one-time low dose of medication to suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive brentuximab vedotin and bendamustine intravenously. Treatment repeats every 21 days for 6 cycles.

18 weeks

6 visits (in-person)

Extension

Participants who respond to treatment may continue to receive single-agent brentuximab vedotin for up to 10 additional cycles.

30 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

2 years

Every 3 months

Treatment Details

Interventions

• Bendamustine Hydrochloride
• Brentuximab Vedotin

Trial Overview The trial tests the combination of brentuximab vedotin (a monoclonal antibody linked to a toxin) and bendamustine (a chemotherapy drug) in patients whose follicular lymphoma has returned or resisted treatment. The goal is to see if this combo is safe and effective in stopping cancer growth by targeting cancer cells directly while preventing them from dividing or spreading.

Participant Groups

Group I: Treatment (brentuximab vedotin, bendamustine) Experimental Treatment 2 Interventions

Patients receive brentuximab vedotin IV over 30 minutes on day 1 and bendamustine IV over 60 minutes on days 1 and 2. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients who respond to combination treatment and do not experience excessive toxicity may continue to receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

Bendamustine Hydrochloride is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)

Approved in European Union as Levact for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)
• Multiple myeloma

Approved in Japan as Ribomustin for:

• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin lymphoma (NHL)

Who Is Running the Clinical Trial?

Joseph Tuscano

Lead Sponsor

Trials

8

Recruited

180+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Findings from Research

Bendamustine demonstrated a 50% overall response rate in patients with refractory or relapsed T-cell lymphomas, with 28% achieving a complete response and 22% a partial response, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with manageable side effects, the most common being neutropenia (30%) and thrombocytopenia (24%), suggesting that bendamustine has an acceptable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. Damaj, G., Gressin, R., Bouabdallah, K., et al.[2022]

Bendamustine, when combined with rituximab, shows strong effectiveness in treating relapsed and refractory indolent lymphoma, with positive results observed in various patient groups, including those who have not previously received rituximab.

Interim results from a phase III trial indicate that the bendamustine and rituximab combination may be a promising alternative to the standard CHOP regimen for treating indolent lymphomas, suggesting a favorable safety and efficacy profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in chronic lymphocytic leukemia and refractory lymphoma. Rummel, MJ.[2015]

Bendamustine is effective as a monotherapy for patients with indolent non-Hodgkin lymphoma (NHL) who are rituximab-refractory, showing high objective response rates in pivotal trials, even among those resistant to standard chemotherapy.

The drug is generally well tolerated, with a low risk of causing hair loss, making it a promising treatment option for patients whose disease has progressed after rituximab-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine: a review of its use in the management of indolent non-Hodgkin lymphoma. Plosker, GL., Carter, NJ.[2021]

In a retrospective study of 48 previously untreated patients with follicular lymphoma, the combination of rituximab and bendamustine led to a remarkable 93% of patients becoming negative for minimal residual disease (MRD) after treatment, indicating its efficacy in eradicating molecular disease.

The study found a 2-year progression-free survival (PFS) rate of 85%, with better outcomes for patients achieving complete response and those with lower FLIPI-2 scores, suggesting that R-bendamustine may effectively improve long-term survival in FL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An Italian Retrospective Study. Galimberti, S., Ciabatti, E., Ercolano, G., et al.[2023]

In a phase 2 trial involving 128 patients with untreated high-risk follicular lymphoma, the combination of ofatumumab and bendamustine showed a complete response (CR) rate of 62%, while adding bortezomib did not significantly improve CR rates, which were 60%.

Both treatment arms had similar rates of severe toxicities, but a higher percentage of patients in the bortezomib group required dose modifications and early treatment discontinuation, indicating that the addition of bortezomib may lead to more treatment challenges without added benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma: CALGB 50904 (Alliance). Blum, KA., Polley, MY., Jung, SH., et al.[2020]

Rolapitant (Varubi) is effective in preventing chemotherapy-induced nausea and vomiting, providing a new option for patients undergoing cancer treatment.

The drug works by blocking neurokinin-1 (NK1) receptors, which play a key role in the vomiting reflex, thus improving the quality of life for patients during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rolapitant (Varubi): A Substance P/Neurokinin-1 Receptor Antagonist for the Prevention of Chemotherapy-Induced Nausea and Vomiting. Goldberg, T., Fidler, B., Cardinale, S.[2020]

In a study of 100 patients with rituximab-refractory indolent B-cell lymphoma, single-agent bendamustine demonstrated a high overall response rate of 75%, with a median duration of response of 9.2 months.

While bendamustine was effective, it also caused significant side effects, including hematologic toxicities like neutropenia (61%) and non-hematologic issues such as nausea (77%) and infections (69%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a Multicenter Study. Kahl, BS., Bartlett, NL., Leonard, JP., et al.[2021]

In a study of 32 classical Hodgkin's lymphoma patients, 47% experienced inadequate control of chemotherapy-induced nausea and vomiting (CINV) with palonosetron and dexamethasone, leading to a switch to netupitant and dexamethasone, which resulted in 53.3% achieving proper CINV control for subsequent cycles.

The switch to NEPA (netupitant/palonosetron) did not increase adverse events compared to the previous treatment, indicating that NEPA is well tolerated and does not interact negatively with standard chemotherapy agents like ABVD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of netupitant/palonosetron and dexamethasone in classical Hodgkin's lymphoma patients with inadequate chemotherapy-induced nausea and vomiting prophylaxis with palonosetron and dexamethasone: a single-center real-life experience. Zilioli, VR., Muzi, C., Minga, P., et al.[2020]

In a study of 61 patients with non-Hodgkin lymphoma undergoing bendamustine-based chemotherapy, both granisetron and palonosetron effectively controlled chemotherapy-induced nausea and vomiting (CINV), with complete control achieved in all patients during the acute phase.

Granisetron monotherapy was found to be as effective and safe as palonosetron combination therapy for preventing delayed CINV, suggesting that granisetron alone could be a cost-effective option for managing CINV in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of antiemetic effects of granisetron and palonosetron in patients receiving bendamustine-based chemotherapy. Uchida, M., Nakamura, T., Makihara, Y., et al.[2019]

In a study involving 36 children undergoing chemotherapy, dexamethasone was found to be the most effective antiemetic, preventing vomiting in 54% of chemotherapy cycles and reducing its intensity in others.

Other antiemetic drugs like Fenactil, Torecan, Aviomarin, and Primperan showed similar efficacy to placebo, indicating they may not be effective in preventing chemotherapy-induced vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assessment of the efficacy of drugs used in prevention of vomiting during anticancer therapy in children]. Gadomski, A., Zmudzka, I., Wójtowicz, H.[2008]

In a dose-escalation study involving 9 patients with relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma, the combination of bendamustine (120 mg/m²) and rituximab (375 mg/m²) was found to be feasible and well tolerated, with no dose-limiting toxicities observed.

The treatment showed promising efficacy, achieving a 100% overall response rate in the higher dose cohort, including five complete responses, indicating that this combination may be effective for aggressive forms of B-NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and pharmacokinetic study of bendamustine hydrochloride in combination with rituximab in relapsed or refractory aggressive B cell non-Hodgkin's lymphoma. Ogura, M., Ando, K., Taniwaki, M., et al.[2015]

In a study of 640 newly diagnosed follicular lymphoma patients, maintenance rituximab (MR) after bendamustine and rituximab (BR) induction improved the duration of response for those who achieved partial remission, while complete remission patients did not show similar benefits.

The safety profile of MR was acceptable, with a fatal adverse event rate of 2.5% after BR, which did not significantly differ between patients receiving MR and those who did not, suggesting that MR is a safe option for patients with partial remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma. Hill, BT., Nastoupil, L., Winter, AM., et al.[2020]

Brentuximab vedotin (Bv) combined with bendamustine (B) showed a high overall response rate of 79% and a complete response rate of 49% in 47 patients with relapsed or refractory classic Hodgkin lymphoma, indicating its efficacy as a treatment option.

The treatment resulted in a median progression-free survival of 18 months and a 2-year overall survival rate of 72%, particularly benefiting patients who achieved a major clinical response and those who underwent stem cell transplantation afterward.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. Iannitto, E., Romano, A., Scalzulli, PR., et al.[2021]

References

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

Results from a prospective, open-label, phase II trial of bendamustine in refractory or relapsed T-cell lymphomas: the BENTLY trial. [2022]

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

Bendamustine in chronic lymphocytic leukemia and refractory lymphoma. [2015]

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

Bendamustine: a review of its use in the management of indolent non-Hodgkin lymphoma. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Combination of Rituximab and Bendamustine as First-Line Treatment Is Highly Effective in the Eradicating Minimal Residual Disease in Follicular Lymphoma: An Italian Retrospective Study. [2023]

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

Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high-risk follicular lymphoma: CALGB 50904 (Alliance). [2020]

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

Rolapitant (Varubi): A Substance P/Neurokinin-1 Receptor Antagonist for the Prevention of Chemotherapy-Induced Nausea and Vomiting. [2020]

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

Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a Multicenter Study. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of netupitant/palonosetron and dexamethasone in classical Hodgkin's lymphoma patients with inadequate chemotherapy-induced nausea and vomiting prophylaxis with palonosetron and dexamethasone: a single-center real-life experience. [2020]

9. Germany pubmed.ncbi.nlm.nih.gov

Comparison of antiemetic effects of granisetron and palonosetron in patients receiving bendamustine-based chemotherapy. [2019]

10. Poland pubmed.ncbi.nlm.nih.gov

[Assessment of the efficacy of drugs used in prevention of vomiting during anticancer therapy in children]. [2008]

11. England pubmed.ncbi.nlm.nih.gov

Feasibility and pharmacokinetic study of bendamustine hydrochloride in combination with rituximab in relapsed or refractory aggressive B cell non-Hodgkin's lymphoma. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma. [2020]

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

Brentuximab vedotin in association with bendamustine in refractory or multiple relapsed Hodgkin lymphoma. A retrospective real-world study. [2021]