Combination Therapy for Mantle Cell Lymphoma

Not currently recruiting at 428 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eastern Cooperative Oncology Group

Must be taking: Anticoagulants, Aspirin

Must not be taking: Zidovudine, Stavudine

Disqualifiers: CNS involvement, AIDS, 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: 22

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores different drug combinations to treat mantle cell lymphoma, a type of blood cancer. It seeks to determine whether adding bortezomib (Velcade) or lenalidomide (Revlimid) to the standard treatment of rituximab (Rituxan) and bendamustine (Treanda) can improve outcomes. The trial includes various treatment paths to identify which combination most effectively stops the cancer. Individuals diagnosed with untreated mantle cell lymphoma who have a measurable sign of the disease might be suitable candidates. As a Phase 2 trial, this research focuses on assessing 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. However, if you are on certain medications like zidovudine or stavudine for HIV, you may need to switch. It's best to discuss your current medications with the trial team to ensure compatibility.

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

Research has shown that the combination of bendamustine and rituximab is generally well-tolerated. More serious side effects, such as a drop in white blood cells, occur in about 21% of cases. However, the overall survival rate at 30 months was 90%, indicating these side effects can be managed.

Studies have demonstrated that the combination of bendamustine, rituximab, and bortezomib is effective without increasing safety concerns. Patients generally tolerated this combination well, with no significant new safety issues reported.

Lenalidomide with rituximab also maintains a good safety record. Long-term results over several years suggest it is effective and has manageable side effects, similar to other standard treatments.

Overall, previous studies have shown these treatments to be safe, with side effects commonly managed in clinical settings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for mantle cell lymphoma because they combine well-known cancer-fighting drugs in new ways to enhance their effectiveness. Unlike other treatments, which often rely on individual drugs like rituximab or bendamustine alone, these combinations integrate them with bortezomib and lenalidomide. Bortezomib adds a unique mechanism by inhibiting proteasomes, which are structures that help cancer cells survive. Meanwhile, lenalidomide boosts the immune system to attack cancer more effectively. By combining these drugs, the treatments aim to tackle the cancer from multiple angles, potentially improving outcomes and providing new hope for patients.

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

Research shows that combining bendamustine and rituximab effectively treats mantle cell lymphoma. Studies have found that 57% of patients using this combination remain alive after seven years. In this trial, one arm will test adding bortezomib to this treatment, which has shown good results in other studies, with 70.3% of patients not experiencing disease progression after two years. Another arm will evaluate adding lenalidomide, although previous research suggests it does not significantly improve outcomes. Overall, these treatments offer strong options for managing mantle cell lymphoma in this trial. ^{2 3 6 7 8}

Who Is on the Research Team?

Mitchell R. Smith, MD, PhD

Principal Investigator

Fox Chase Cancer Center

Are You a Good Fit for This Trial?

This trial is for older adults with untreated Mantle Cell Lymphoma (MCL). Participants must have proper liver function, no central nervous system involvement, and not be pregnant. HIV-positive patients can join if they meet specific health criteria. Contraception use is required, and there should be no history of severe allergies to the drugs used or conditions that could affect study participation.

Inclusion Criteria

I can take care of myself and perform daily activities.

Patient agrees that if randomized to Arms C or D, and proceed onto Arms G or H, they must register into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®

People with HIV can participate if they meet specific requirements.

Exclusion Criteria

Patient is living outside the US

I have no cancer history except for certain skin cancers, cervical cancer in situ, or any cancer cured over 5 years ago.

My disease was confirmed by CT scan or similar, not just a PET scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive induction therapy comprising rituximab and bendamustine, with or without bortezomib, repeated every 4 weeks for 6 courses

24 weeks

6 visits (in-person)

Maintenance

Participants receive maintenance therapy with rituximab, with or without lenalidomide, every 8 weeks for 2 years

104 weeks

13 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Every 3 months for 2.5 years, every 6 months up to 10 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Bendamustine Hydrochloride
• Bortezomib
• Lenalidomide
• Rituximab

Trial Overview

The trial tests a combination of rituximab with bendamustine hydrochloride and bortezomib versus rituximab with lenalidomide in treating MCL. It aims to discover which drug combo is more effective at stopping cancer growth by either killing cancer cells directly or cutting off their blood supply.

How Is the Trial Designed?

Group I: Induction: (D) Bendamustine + Rituximab + Bortezomib then Maintenance: (H) Lenalidomide + Rituximab Experimental Treatment 4 Interventions

Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Group II: Induction: (C) Bendamustine + Rituximab then Maintenance: (G) Lenalidomide + Rituximab Experimental Treatment 3 Interventions

Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising lenalidomide orally (PO) daily on days 1-21 every 4 weeks and rituximab IV every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Group III: Induction: (B) Bendamustine + Rituximab + Bortezomib then Maintenance: (F) Rituximab Experimental Treatment 3 Interventions

Patients receive induction therapy comprising rituximab IV on day 1, bendamustine hydrochloride IV over 60 minutes on days 1-2 and bortezomib IV subcutaneously (SC) on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Group IV: Induction: (A) Bendamustine + Rituximab then Maintenance: (E) Rituximab Experimental Treatment 2 Interventions

Patients receive induction therapy comprising rituximab IV on day 1 and bendamustine hydrochloride IV over 60 minutes on days 1-2. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to maintenance treatment. Patients receive maintenance therapy comprising rituximab IV on day 1. Courses repeat every 8 weeks for 2 years 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?

Eastern Cooperative Oncology Group

Lead Sponsor

Trials

272

Recruited

153,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a network meta-analysis of three randomized controlled trials involving 1459 patients with newly diagnosed mantle-cell lymphoma (MCL) ineligible for intensive therapy, the combination of ibrutinib plus bendamustine and rituximab (Ibru + BR) significantly improved progression-free survival (PFS) compared to other regimens like VR-CAP and R-CHOP.

Ibru + BR had a 94.9% probability of being the best treatment option for prolonging PFS, with no significant differences in adverse events compared to the other treatment regimens, indicating its efficacy and safety for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Sheng, Z., Wang, L.[2023]

The combination of bendamustine and rituximab (BR) showed a high overall response rate of 90% in 63 patients with mantle cell or low-grade lymphomas, with a complete remission rate of 60%.

The median progression-free survival was 24 months, indicating that BR is an effective treatment option for patients in their first to third relapse or refractory to previous treatments, although myelosuppression was noted as a significant side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. Rummel, MJ., Al-Batran, SE., Kim, SZ., et al.[2022]

In a study involving 549 patients with advanced indolent lymphoma, bendamustine plus rituximab significantly improved median progression-free survival (69.5 months) compared to R-CHOP (31.2 months), indicating it may be a more effective first-line treatment.

Bendamustine plus rituximab was better tolerated than R-CHOP, with significantly lower rates of side effects such as alopecia, hematological toxicity, infections, and peripheral neuropathy, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Rummel, MJ., Niederle, N., Maschmeyer, G., et al.[2022]

The RBAC500 regimen, which combines rituximab, bendamustine, and low-dose cytarabine, showed a high efficacy in treating elderly patients with mantle cell lymphoma, with 91% of patients achieving a complete response after treatment.

While the treatment did not meet the predefined safety criteria due to manageable hematological toxicities, such as neutropenia and thrombocytopenia, it was deemed effective and safe enough to warrant further investigation in phase 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Visco, C., Chiappella, A., Nassi, L., et al.[2018]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/30811293/

First-Line Treatment of Patients With Indolent Non-Hodgkin ...

Conclusion: Overall, BR demonstrated better long-term disease control than R-CHOP/R-CVP and should be considered as a first-line treatment ...

2.

ashpublications.org

ashpublications.org/blood/article/142/Supplement%201/300/499491/Multicenter-Study-of-Mantle-Cell-Lymphoma-Outcomes

Multicenter Study of Mantle Cell Lymphoma Outcomes ...

Conclusion: In this multicenter retrospective study, initiation of 1L BR (with or without rituximab maintenance) resulted in a 7-year OS of 57%.

3.

ascopubs.org

ascopubs.org/doi/10.1200/JCO-25-00690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ...

The addition of acalabrutinib to bendamustine plus rituximab significantly improved progression-free survival (PFS) compared with placebo and ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11326663/

Clinical Outcome of Patients Receiving Rituximab in ...

Our study demonstrated that patients on R-Benda had good clinical outcomes, with the vast majority living beyond 50 months. Moreover, 76.1% had ...

5.

ar.iiarjournals.org

ar.iiarjournals.org/content/42/12/6083

Bendamustine Plus Rituximab for Mantle Cell Lymphoma

The median PFS was 12.8 months, and the three-year OS rate was 66.8%±16.2%. Conclusion: BR is an effective regimen for both newly-diagnosed and relapsed or ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11370709/

Efficacy and Safety of Bendamustine-Rituximab as ...

At 30 months, PFS was 74.8% and overall survival was 90%. Grade 3-4 neutropenia occurred in 21% of patients. Infection-related adverse events ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10405197/

Long-term follow-up of rituximab plus bendamustine and ...

In 57 previously untreated elderly patients with mantle cell lymphoma (MCL), R-BAC was associated with a complete remission rate of 91% and 2-year progression- ...

8.

haematologica.org

haematologica.org/article/view/haematol.2023.284896

Safety and efficacy of acalabrutinib plus bendamustine and ...

Overall response was 94.4% and 85.0% in the TN and R/R cohorts, respectively; complete response rates were 77.8% and 70.0%, respectively. After ...