Ofatumumab + Bendamustine +/- Bortezomib for Follicular Lymphoma

No longer recruiting at 111 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Corticosteroids, Zidovudine, Stavudine

Disqualifiers: CNS involvement, Active hepatitis B/C, 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: 14

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of drugs can more effectively treat follicular lymphoma, a type of non-Hodgkin lymphoma affecting the lymphatic system. Researchers aim to determine if combining ofatumumab (a monoclonal antibody) and bendamustine (a chemotherapy drug) with bortezomib (a proteasome inhibitor) enhances treatment efficacy. These drugs target the growth and spread of cancer cells. Individuals with untreated follicular non-Hodgkin lymphoma who have certain risk factors, such as large lymph nodes or multiple affected areas, may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that no corticosteroids are allowed, except for low-dose maintenance therapy for non-cancer conditions. It's best to discuss your current medications with the trial team to get specific guidance.

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

A previous study found the combination of ofatumumab and bendamustine to be safe. Patients tolerated the treatment well, with no severe side effects reported.

Adding bortezomib to ofatumumab and bendamustine did not significantly increase serious side effects. This suggests that patients with follicular lymphoma generally tolerate the treatment well.

However, as this trial is in an early stage, researchers are still studying the complete safety profile. Participants should know that while current results are promising, ongoing research will continue to closely monitor safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine existing therapies in innovative ways to potentially enhance their effectiveness against follicular lymphoma. Ofatumumab is a monoclonal antibody that specifically targets CD20 proteins on the surface of cancerous B cells, helping the body's immune system to destroy them. Bendamustine hydrochloride is a chemotherapy that works by damaging the DNA of cancer cells, preventing them from dividing. Adding bortezomib, a proteasome inhibitor, may increase the treatment's potency by disrupting the cancer cells' ability to manage protein waste, leading to cell death. This combination aims to improve patient outcomes by attacking the cancer from multiple angles, offering hope for those who may not respond well to standard treatments.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research has shown that combining ofatumumab with bendamustine results in about 42.9% of patients experiencing disease progression, and 14.3% died during the study. However, other studies have reported a complete disappearance of cancer in about 50% of patients with this combination. In this trial, one arm will test ofatumumab and bendamustine, while another will add bortezomib to these drugs. Studies suggest that adding bortezomib does not improve progression-free survival or overall survival. In one study, the overall response to the three-drug combination (ofatumumab, bendamustine, and bortezomib) was 91%, with 60% achieving a complete response and 75.6% not experiencing disease progression for two years. Despite these results, adding bortezomib did not significantly benefit patients with high-risk follicular lymphoma. ^{2 3 6 7 8}

Who Is on the Research Team?

Kristie A Blum

Principal Investigator

Alliance for Clinical Trials in Oncology

Are You a Good Fit for This Trial?

This trial is for adults with untreated follicular non-Hodgkin lymphoma, grades 1-3a. Participants must have certain risk factors like age over 60 or involvement of more than four nodal sites. They should not have had previous cancer treatments and must not be pregnant or nursing, agreeing to use contraception if necessary. People with HIV can join if they meet specific health criteria.

Inclusion Criteria

I am not pregnant or nursing and will use effective birth control during the study.

Granulocytes >= 1,000/uL

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Patients receive ofatumumab and bendamustine hydrochloride, with or without bortezomib, for up to 6 cycles

6 cycles (approximately 30 weeks)

6 visits (in-person)

Maintenance Therapy

Patients receive maintenance therapy with ofatumumab, with or without bortezomib, every 56 days for up to 4 courses

32 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 4 months for 2 years, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine Hydrochloride
• Bortezomib
• Ofatumumab

Trial Overview The study tests how well the combination of ofatumumab and bendamustine hydrochloride works compared to adding bortezomib in treating this type of lymphoma. Ofatumumab targets cancer cells, while bendamustine hydrochloride and bortezomib work to stop cancer growth by killing cells or blocking enzymes needed for cell growth.

How Is the Trial Designed?

Group I: Arm B (ofatumumab, bendamustine hydrochloride, bortezomib) Experimental Treatment 6 Interventions

INDUCTION: Patients receive ofatumumab IV over 2-8 hours on day 1, bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2, and bortezomib IV over 3-5 seconds or SC on days 1, 8, 15, and 22. Treatment repeats every 35 days for up to 6 courses. Patients without disease progression continue on to maintenance therapy. MAINTENANCE: Beginning 8 weeks after the start of induction course 6, patients receive ofatumumab IV over 2-8 hours on day 1 and bortezomib IV over 3-5 seconds or SC on days 1, 8, 15, and 22. Treatment repeats every 56 days for up to 4 courses.

Group II: Arm A (ofatumumab, bendamustine hydrochloride) Experimental Treatment 5 Interventions

INDUCTION: Patients receive ofatumumab IV over 2-8 hours on day 1 and bendamustine hydrochloride IV over 30-60 minutes on days 1 and 2. Treatment repeats every 35 days for up to 6 courses. Patients without disease progression continue on to maintenance therapy. MAINTENANCE: Beginning 8 weeks after the start of induction course 6, patients receive ofatumumab IV over 2-8 hours on day 1. Treatment repeats every 56 days for up to 4 courses.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Bendamustine demonstrated a high objective response rate of 74.3% in 99 patients with relapsed/refractory Hodgkin and non-Hodgkin lymphoma, indicating its efficacy as a salvage treatment after multiple lines of chemotherapy.

The most common side effects included lymphopenia, anemia, and neutropenia, with serious side effects occurring in a minority of patients, suggesting that while bendamustine is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. Karadurmus, N., Paydas, S., Esin, E., et al.[2022]

In a study of 49 patients with newly diagnosed multiple myeloma, the combination therapy of bortezomib, bendamustine, and prednisone showed a high response rate, with 82% of patients responding after at least one treatment cycle.

The treatment was well tolerated and demonstrated promising progression-free survival (PFS) and overall survival (OS) rates, particularly in patients with normal or mild renal dysfunction, indicating its efficacy across varying levels of renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with newly diagnosed/untreated multiple myeloma. Pönisch, W., Holzvogt, B., Plötze, M., et al.[2021]

In a study involving 73 patients with relapsed or refractory follicular lymphoma, the combination of bortezomib, bendamustine, and rituximab achieved an impressive overall response rate of 88%, with 53% of patients experiencing a complete response.

The treatment demonstrated a median progression-free survival of 14.9 months, and while there were manageable toxicities, including myelosuppression, the overall safety profile was acceptable for patients undergoing this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. Fowler, N., Kahl, BS., Lee, P., et al.[2020]

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]

Citations

1. onclive.com onclive.com/view/ofatumumab-combo-falls-short-in-indolent-nonhodgkin-lymphoma

Ofatumumab Combo Falls Short in Indolent Non-Hodgkin ... Adding ofatumumab (Arzerra) to bendamustine (Treanda) failed to improve progression-free survival in patients with indolent B-cell non-Hodgkin ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6693706/

Phase II Study of Bendamustine and Ofatumumab in ... Studies of the combination of bendamustine and rituximab in elderly patients have demonstrated a complete response rate of approximately 50%, and the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01077518?cond=%22Follicular%20Lymphoma%22&intr=%22pharmaceutical%20solutions%22&viewType=Table&rank=7&tab=results

Study Results | Ofatumumab Bendamustine Combination ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33448893/

Efficacy and safety of ofatumumab and bendamustine ... Overall, 42.9% progressed and 14.3% died during the study. Thus, ofatumumab in combination with bendamustine, followed by ofatumumab maintenance ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/66/NCT01458366/Prot_SAP_000.pdf

Phase I/II Study of Bendamustine in Combination with ... Based on these studies, it has been established that ofatumumab is safe to give as a single agent in B cell lymphomas. 1.2.3. Adverse Events Noted in Follicular ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01458366

NCT01458366 | Phase I/II Study of Bendamustine in ... Bendamustine has shown impressive activity and a favorable safety profile when used in combination with rituximab and other cytotoxic drugs: Weide R et al (2007) ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01108341

NCT01108341 | Study to Evaluate the Efficacy and Safety ... The primary objective of the study is to determine the efficacy, as measured by overall response (complete response + partial response) of bendamustine in ...

8. ohsu.edu ohsu.edu/sites/default/files/2025-04/OHSU-HS-MPS-Bendamustine-03-25.pdf

Bendamustine: Treanda®; Bendeka®; Belrapzo®; Vivimusta Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: ...