Ofatumumab + Bendamustine +/- Bortezomib for Follicular Lymphoma

Recruiting at 104 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

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

135 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies how well ofatumumab and bendamustine hydrochloride with or without bortezomib works in treating patients with untreated follicular non-Hodgkin lymphoma. Monoclonal antibodies, such as ofatumumab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as bendamustine hydrochloride, 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. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bortezomib may also stop the growth of cancer cells by blocking blood flow to the tumor. It is not yet known whether ofatumumab and bendamustine hydrochloride are more effective with bortezomib in treating patients with follicular non-Hodgkin lymphoma.

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.

What data supports the effectiveness of the drug combination of Ofatumumab, Bendamustine, and Bortezomib for treating follicular lymphoma?

Research shows that the combination of bendamustine and ofatumumab has a high response rate of 90% in patients with indolent B cell non-Hodgkin's lymphoma, which is similar to other effective treatments. Additionally, a study involving bendamustine, bortezomib, and rituximab in relapsed lymphoma patients showed promising results, suggesting potential effectiveness of similar combinations. ^{1 2 3 4 5}

How is the drug combination of Ofatumumab, Bendamustine, and Bortezomib unique for treating follicular lymphoma?

This drug combination is unique because it combines Ofatumumab, a human anti-CD20 antibody, with Bendamustine, a chemotherapy drug, and Bortezomib, a proteasome inhibitor, to potentially enhance treatment effectiveness for follicular lymphoma. This combination aims to improve response rates and manage high-risk cases by leveraging the different mechanisms of action of each drug. ^{1 2 3 6 7}

Research Team

Kristie A Blum

Principal Investigator

Alliance for Clinical Trials in Oncology

Eligibility Criteria

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

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

Granulocytes >= 1,000/uL

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma. [2019]

2. 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]

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

The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. [2021]

4. Poland pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022]

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

Phase II Study of Bendamustine and Ofatumumab in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy. [2020]

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

Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Bendamustine and prednisone in combination with bortezomib (BPV) in the treatment of patients with newly diagnosed/untreated multiple myeloma. [2021]