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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining the drug Rituximab (a type of immunotherapy) with chemotherapy can better control Mantle Cell Lymphoma (MCL), a type of blood cancer, in untreated individuals. The treatment includes cycles of various chemotherapy medications with Rituximab, followed by ongoing Rituximab therapy for those in remission. The trial seeks participants diagnosed with MCL who have not yet started treatment and can commit to a long-term study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in MCL treatment.

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.

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

Research has shown that adding rituximab to chemotherapy is generally safe and can improve outcomes for people with mantle cell lymphoma. Studies have found that this combination increases response rates and overall survival. Most patients tolerate rituximab well, though some may experience mild to moderate side effects like fever or chills.

The chemotherapy drugs used in this study have been part of other treatments before. Common side effects include nausea, tiredness, and low blood cell counts, but supportive care can usually manage these. Overall, the treatment under study has shown promise in helping patients while maintaining a safety profile similar to other chemotherapy options. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for mantle cell lymphoma because it combines Rituximab with a unique chemotherapy regimen known as R-MACLO/IVAM. Unlike standard treatments that often use simpler chemotherapy combinations, this approach strategically alternates different sets of drugs across treatment cycles to target cancer cells more effectively. The use of Rituximab as a maintenance therapy is also noteworthy, as it helps maintain remission over a longer period, potentially enhancing long-term outcomes. This innovative combination holds promise for improving both survival rates and quality of life for patients.

What evidence suggests that Rituximab and combination chemotherapy could be effective for Mantle Cell Lymphoma?

Research has shown that combining rituximab with chemotherapy can extend the lives of patients with mantle cell lymphoma (MCL). In this trial, participants in the R-MACLO/IVAM group will receive rituximab and chemotherapy, followed by rituximab maintenance therapy. This ongoing treatment after initial therapy has been particularly beneficial for older patients unable to undergo stem cell transplants. Studies indicate that the R-MACLO/IVAM chemotherapy regimen, followed by maintenance therapy, can lead to long-lasting remissions. Real-world evidence supports this approach, with patients experiencing significant improvements in survival and disease control. Overall, this combination treatment shows promise for individuals with newly diagnosed MCL. ^{6 7 8 9 10}

Who Is on the Research Team?

Izidore Lossos, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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

Women of childbearing potential must have a negative pregnancy test within 72 hours of entering into the study. Males and females must agree to use adequate birth control if conception is possible during the study. Women must avoid pregnancy and men avoid fathering children while in the study

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Participants in this group will receive four 21-day cycles of combination R-MACLO/IVAM induction therapy, followed by Rituximab maintenance therapy as follows: Induction Therapy: * Cycles 1 and 3: Rituximab, Doxorubicin, Vincristine, Cyclophosphamide, Methotrexate, Leucovorin and Granulocyte-colony stimulating factor (G-CSF) * Cycles 2 and 4: Rituximab, Cytarabine, Ifosfamide, Mesna, Etoposide, and G-CSF. Maintenance Therapy: Rituximab: For study participants in complete remission. Every 6 months for up to 3 years. Total participation duration is about 4 years. Participants will be followed for survival.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33735476/

R-MACLO-IVAM regimen followed by maintenance therapy ... R-MACLO-IVAM regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma - Long term follow up results.

2. ashpublications.org ashpublications.org/bloodadvances/article/9/20/5382/546349/Real-world-outcomes-of-brexucabtagene-autoleucel

Real-world outcomes of brexucabtagene autoleucel for ... One-year overall survival and progression-free survival rates were 76% and 63%, respectively. One-year cumulative incidence of nonrelapse ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00450801

R-MACLO-IVAM and Thalidomide in Untreated Mantle Cell ... PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy followed by thalidomide works in treating patients ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ajh.26163

R‐MACLO‐IVAM regimen followed by maintenance ... R-MACLO-IVAM regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma - Long term follow up results ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4439262/

Updated survival analysis of two sequential prospective trials ... Thirty-five patients completed at least 2 cycles of chemotherapy; 34 (94%) achieved a CR. After a median follow-up of 74.4 months, the 5-year PFS was 51% (95% ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00878254?cond=%22Hodgkin's%20Granuloma%22&intr=%22vitamins%22&viewType=Table&rank=10

Rituximab and Combination Chemotherapy in Treating Patients ... 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10492741/

The addition of rituximab to chemotherapy improves overall ... The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma—a pooled trials analysis.

8. ohsu.edu ohsu.edu/sites/default/files/2024-02/OHSU%20HS-MRxM-Rituximab-IV%20%28E%29-01-24.pdf

Rituximab: Rituxan®, Truxima®, Ruxience™, Riabni™ A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product. (MabThera®) in Subjects ...

9. cancernetwork.com cancernetwork.com/view/addition-rituximab-combination-chemotherapy-improves-response-rates-mantle-cell-and-other-lymphomas

Addition of Rituximab to Combination Chemotherapy ... Addition of Rituximab to Combination Chemotherapy Improves Response Rates in Mantle Cell and Other Lymphomas ... Safe and Effective in Follicular Lymphoma.

10. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)00237-3/fulltext

Treatment Landscape of Relapsed/Refractory Mantle Cell ... In this report, we provide an updated literature review that covers recent clinical data about the safety and efficacy of novel therapies for the management of ...