Combination Therapy for Mantle Cell Lymphoma

Recruiting at 417 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eastern Cooperative Oncology Group

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

373 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as bendamustine hydrochloride, also work in different ways to kill cancer cells or stop them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. It is not yet known whether giving rituximab together with bendamustine and bortezomib is more effective than rituximab and bendamustine, followed by rituximab alone or with lenalidomide in treating mantle cell lymphoma. PURPOSE: This randomized phase II trial studies rituximab, bortezomib, bendamustine, and lenalidomide in treating previously untreated older patients with mantle cell lymphoma.

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.

What data supports the effectiveness of the drug combination therapy for Mantle Cell Lymphoma?

Research shows that the combination of bendamustine and rituximab is effective for treating mantle cell lymphoma, with studies indicating high response rates and favorable outcomes. Additionally, the combination of bendamustine, bortezomib, and rituximab has shown promising results, with a significant number of patients achieving a positive response. ^{1 2 3 4 5}

What safety data exists for the combination therapy for Mantle Cell Lymphoma?

The combination of bendamustine, bortezomib, and rituximab has been studied in patients with relapsed or refractory mantle cell lymphoma. In a study, eight patients experienced serious side effects, including one case of severe infection (sepsis). Common mild to moderate side effects included nausea, nerve pain, tiredness, constipation, and fever. ^{1 2 3 4 6}

What makes the combination therapy of Bendamustine, Bortezomib, and Rituximab unique for treating mantle cell lymphoma?

This combination therapy is unique because it combines three drugs that work together to enhance effectiveness and is specifically designed for patients with relapsed or hard-to-treat mantle cell lymphoma, showing promising results in improving progression-free survival. ^{1 2 3 5 7}

Research Team

Mitchell R. Smith, MD, PhD

Principal Investigator

Fox Chase Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States 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. [2022]

2. 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]

3. Greece pubmed.ncbi.nlm.nih.gov

Bendamustine Plus Rituximab for Mantle Cell Lymphoma: A Korean, Multicenter Retrospective Analysis. [2022]

4. England 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. [2022]

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

Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. [2022]

6. England 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. [2018]

7. England 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. [2023]