Rituximab + Bendamustine/Cytarabine for Mantle Cell Lymphoma

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Antiretrovirals

Disqualifiers: Pregnancy, Breastfeeding, HIV, 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: 12

Duration: 24 weeks

23 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

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, Bendamustine, and Cytarabine for Mantle Cell Lymphoma?

Research shows that the combination of rituximab, bendamustine, and cytarabine is effective in treating mantle cell lymphoma, especially in older patients or those who cannot undergo intensive treatments. Studies indicate that this combination is highly active, although it may have some side effects related to blood cell counts. ^{1 2 3 4 5}

Is the combination of Rituximab, Bendamustine, and Cytarabine safe for treating mantle cell lymphoma?

The combination of Rituximab, Bendamustine, and Cytarabine has shown high activity in treating mantle cell lymphoma, but it is associated with significant blood-related side effects. The combination of Rituximab and Bendamustine alone is considered effective with a more favorable safety profile. ^{1 2 3 6 7}

How is the drug combination of Rituximab, Bendamustine, and Cytarabine unique for treating mantle cell lymphoma?

This drug combination is unique because it includes low-dose cytarabine, which is added to the already effective combination of rituximab and bendamustine, specifically for elderly patients or those who cannot undergo intensive treatments. It aims to balance high activity against the cancer with manageable side effects. ^{1 2 3 5 6}

What is the purpose of this trial?

Mantle cell lymphoma (MCL) is not curable with conventional therapy. This study sought to improve upon standard of care in newly diagnosed, untreated MCL patients who were transplant-eligible using drugs already established as active in MCL. The combination of Rituximab-Bendamustine followed by Rituximab-Cytarabine (RB/RC) was expected to maximize pre-ASCT complete response (CR) rate compared to historical rates approximating 55% with tolerable toxicity.

Research Team

Philippe Armand, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for newly diagnosed, untreated patients with Mantle Cell Lymphoma who are eligible for a stem cell transplant. They must have measurable disease and agree to pathology review at specified hospitals. Excluded are those allergic to rituximab, on other trials, HIV positive on antiretrovirals, pregnant or breastfeeding women, and those with uncontrolled illnesses or prior lymphoma treatment.

Inclusion Criteria

Measurable disease

Mandatory pathologic review of the diagnostic specimen(s) at Brigham and Women's Hospital or Massachusetts General Hospital

I am eligible for a stem cell transplant.

Exclusion Criteria

You are currently taking part in another clinical trial.

I do not have any unmanaged ongoing illnesses.

You are allergic to rituximab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 3 cycles of Rituximab-Bendamustine followed by 3 cycles of Rituximab-Cytarabine

24 weeks

6 cycles of treatment, each cycle lasting 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

13 months

Every 6 months until relapse, death, or 5 years

Stem Cell Mobilization and ASCT

Stem cell mobilization and collection, followed by autologous stem cell transplantation

Up to 3 months post-treatment

Treatment Details

Interventions

• Bendamustine
• Cytarabine
• Rituximab

Trial Overview The study tests Rituximab-Bendamustine followed by Rituximab-Cytarabine in MCL patients to see if it can increase the rate of complete response before stem cell transplantation compared to the historical rate of 55%, while keeping side effects manageable.

Participant Groups

Group I: RB/RC Experimental Treatment 3 Interventions

Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to: 1. 2 g/m2 for age \>60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity; 2. 1.5 g/m2 for age \>60 years old AND creatinine 114.9-176.8 lmol/l, or for age \>60 years old AND pre-existing neurotoxicity; 3. 1 g/m2 for age \> 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity. Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study.

Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Findings from Research

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]

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]

References

1. 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]

2. 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]

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

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Rituximab and Bendamustine (BR) Compared with Rituximab, Bendamustine, and Cytarabine (R-BAC) in Previously Untreated Elderly Patients with Mantle Cell Lymphoma. [2021]

7. 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]