Rituximab + Bendamustine/Cytarabine for Mantle Cell Lymphoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments to improve outcomes for people with mantle cell lymphoma (MCL), a type of blood cancer that's difficult to cure with standard treatments. The study aims to determine if combining the drugs Rituximab, Bendamustine (a chemotherapy drug), and Cytarabine (another chemotherapy drug) can enhance the chances of a better response before a stem cell transplant. People recently diagnosed with MCL, who have not yet received treatment and are eligible for a stem cell transplant, may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to advancements in MCL treatment.

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.

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

Research has shown that the combination of rituximab, bendamustine, and cytarabine is generally well-tolerated by patients with mantle cell lymphoma. Studies have found that using bendamustine and rituximab together is safe for this condition. However, adding cytarabine can increase risks. For example, one study found that 13% of patients developed a second cancer after starting treatment. Despite this, the treatment is effective, and many patients find the side effects manageable. Discussing potential risks and benefits with a healthcare provider is important before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Rituximab, Bendamustine, and Cytarabine for treating Mantle Cell Lymphoma because it offers a fresh approach compared to the conventional therapies. While the standard treatments often rely on chemotherapy or targeted therapy alone, this combination leverages Rituximab, an antibody targeting CD20 on B-cells, with the chemotherapeutic agents Bendamustine and Cytarabine. This strategic combination aims to enhance the effectiveness by potentially overcoming resistance and providing a more robust attack on cancer cells. Additionally, the use of adjusted doses of Cytarabine based on age and kidney function could optimize safety and reduce side effects for older patients.

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

In this trial, participants will receive a combination of Rituximab, Bendamustine, and Cytarabine, which research has shown to be promising for treating mantle cell lymphoma (MCL). Studies have found that adding a high dose of Cytarabine to Rituximab and Bendamustine can improve outcomes for patients eligible for a stem cell transplant. This combination has proven effective in previous MCL patients, demonstrating good results and manageable side effects. Additionally, this drug mix is known for achieving a strong response in people with MCL. These findings suggest it could be a good option for those newly diagnosed with this condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Philippe Armand, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32126141/

Rituximab/bendamustine and rituximab/cytarabine ... The addition of high-dose cytarabine to rituximab/bendamustine (RB) induction could improve outcomes for transplant-eligible patients with mantle cell lymphoma ...

2. medivizor.com medivizor.com/blog/SampleLibrary/non-hodgkin-lymphoma/rituximab-bendamustine-and-low-dose-cytarabine-treatment-for-elderly-patients-with-mantle-cell-lymphoma/

Rituximab, bendamustine, and low-dose cytarabine ... The study concluded that this treatment is effective at treating elderly patients with mantle cell lymphoma, but has some adverse events. Some ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23401442/

Combination of rituximab, bendamustine, and cytarabine ... The combination of bendamustine (B) and rituximab (R) is efficacious, with favorable toxicity in mantle-cell lymphoma (MCL).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01661881?term=AREA%5BConditionSearch%5D(Malignancy)%20AND%20AREA%5BBasicSearch%5D(rituximab)%20AND%20AREA%5BOverallStatus%5D(RECRUITING%20OR%20ENROLLING_BY_INVITATION%20OR%20ACTIVE_NOT_RECRUITING%20OR%20AVAILABLE)&rank=6&tab=results

Study Results | Rituximab/Bendamustine ... These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable. Describes trials without FDA-defined phases ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04115631

Study Details | NCT04115631 | A Comparison of Three ... This phase II trial compares three chemotherapy regimens consisting of bendamustine, rituximab, high dose cytarabine, and acalabrutinib and studies how well ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01661881

Study Details | NCT01661881 | Rituximab/Bendamustine + ... This study sought to improve upon standard of care in newly diagnosed, untreated MCL patients who were transplant-eligible using drugs already established as ...

7. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper198687.html

Rituximab/Cytarabine (BR/RC) Induction Therapy for ... 11 patients (13%) developed a second malignancy following treatment initiation (n=3 myelodysplastic syndrome/acute myeloid leukemia, n=1 each: ...