Rituximab + Chemotherapy for Mantle Cell Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Disqualifiers: Active malignancies, Cardiac failure, HIV/AIDS, Hepatitis, CNS involvement, 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: Unknown

Duration: 12 weeks

25 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigator(s) hypothesize that Rituximab together with combination chemotherapy, followed by Rituximab maintenance therapy, will provide better disease control with improved response rates and overall survival in patients with previously untreated Mantle Cell Lymphoma (MCL).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Rituximab + Chemotherapy for treating mantle cell lymphoma?

Research shows that adding rituximab to chemotherapy significantly improved the time patients lived without the disease getting worse, from about 15 months to nearly 30 months. Additionally, rituximab maintenance therapy after initial treatment improved both the time patients lived without the disease worsening and overall survival. ^{1 2 3 4 5}

Is Rituximab combined with chemotherapy safe for treating mantle cell lymphoma?

Rituximab combined with chemotherapy has been studied for safety in mantle cell lymphoma and other conditions. Some studies reported serious side effects like infections and blood-related issues, but many patients tolerated the treatment well. Common side effects included nausea, fatigue, and fever. ^{1 3 5 6 7}

How does the drug Rituximab combined with chemotherapy differ from other treatments for mantle cell lymphoma?

Rituximab combined with chemotherapy is unique because it significantly improves progression-free survival in mantle cell lymphoma patients compared to chemotherapy alone, doubling the median time before the disease progresses. This combination leverages rituximab's ability to target B-cells, which are involved in this type of lymphoma, enhancing the effectiveness of standard chemotherapy regimens. ^{1 2 8 9 10}

Research Team

Izidore Lossos, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for adults over 18 with previously untreated Mantle Cell Lymphoma. Participants must have measurable disease, proper liver and kidney function, not be pregnant or breastfeeding, agree to use birth control, and have a life expectancy of more than 6 months. Those with severe heart issues, other active cancers (except certain skin/cervix cancers), HIV/AIDS, hepatitis infection or CNS involvement cannot join.

Inclusion Criteria

I have mantle cell lymphoma and have not received any treatment for it.

Life expectancy greater than 6 months

I am older than 18 years.

Exclusion Criteria

My heart's pumping ability is significantly reduced.

I have hepatitis or hepatitis B virus infection.

I have had treatments like chemotherapy for my mantle cell lymphoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Rituximab in combination with chemotherapy over four 21-day cycles

12 weeks

Maintenance Therapy

Rituximab maintenance therapy for participants in complete remission, administered every 6 months

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 8 years

Treatment Details

Interventions

• Combination Chemotherapy
• Rituximab

Trial Overview The study tests Rituximab combined with chemotherapy drugs (Cyclophosphamide, Cytarabine, Doxorubicin etc.), followed by maintenance therapy with Rituximab alone. The goal is to see if this regimen improves response rates and overall survival in patients who haven't been treated for MCL before.

Participant Groups

Group I: R-MACLO/IVAM Experimental Treatment 11 Interventions

Four 21-day cycles, followed by Maintenance Therapy as follows: * Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin, and G-CSF per study protocol. * Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF per study protocol. * Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years, per study protocol.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

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]

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]

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

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]

Rituximab is a highly effective monoclonal antibody for treating various B-cell lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, demonstrating a strong activity with low toxicity.

The combination of rituximab with chemotherapy (R-CHOP) has shown the highest efficacy reported for any chemotherapy regimen in treating diffuse large B-cell lymphoma and follicular lymphoma, although some patients may still be resistant to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. Coiffier, B.[2022]

References

1. Italy pubmed.ncbi.nlm.nih.gov

The addition of rituximab to fludarabine and cyclophosphamide chemotherapy results in a significant improvement in overall survival in patients with newly diagnosed mantle cell lymphoma: results of a randomized UK National Cancer Research Institute trial. [2018]

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

Rituximab maintenance therapy for mantle cell lymphoma: A systematic review and meta-analysis. [2019]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Activity and safety of combined rituximab with chlorambucil in patients with mantle cell lymphoma. [2015]

5. Italy pubmed.ncbi.nlm.nih.gov

First-line treatment with rituximab-hyperCVAD alternating with rituximab-methotrexate-cytarabine and followed by consolidation with 90Y-ibritumomab-tiuxetan in patients with mantle cell lymphoma. Results of a multicenter, phase 2 pilot trial from the GELTAMO group. [2021]

6. 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]

7. 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]

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

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. [2015]

9. 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]

10. England pubmed.ncbi.nlm.nih.gov

Rituximab therapy in malignant lymphoma. [2022]