Chemotherapy Combinations for Mantle Cell Lymphoma

Not currently recruiting at 532 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Pregnancy, Active infections, Cardiac disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares three chemotherapy combinations to determine which is most effective for people with newly diagnosed mantle cell lymphoma, a type of blood cancer. The treatments being tested include combinations of drugs such as bendamustine, rituximab, cytarabine, and acalabrutinib (Calquence), each targeting cancer cells in different ways. The study aims to assess whether these combinations are more effective than the standard treatment. It is suitable for those with untreated mantle cell lymphoma who are seeking new treatment options. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing an opportunity to explore promising new therapies.

Will I have to stop taking my current medications?

The trial requires that patients switch from proton pump inhibitors to an alternative drug before starting acalabrutinib. Additionally, patients must not take strong or moderate CYP3A inhibitors or inducers within 7 days before the first dose of the study drug. If you are on these medications, you may need to stop or switch them.

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

Earlier studies have shown that the combination of bendamustine and rituximab is effective for patients with mantle cell lymphoma, with mostly mild side effects. Research indicates that this combination is generally safe. Some patients experienced side effects, but they were usually manageable.

When acalabrutinib was added to bendamustine and rituximab, studies found it to be safe overall. Patients tolerated the three drugs well, with most side effects not being serious. However, some experienced side effects like low blood cell counts, which doctors closely monitored.

Adding cytarabine to the mix has also been studied. Initial findings suggest this combination remains safe, but it may increase the risk of side effects like low blood cell counts and infections. Doctors manage these risks with regular check-ups and supportive care.

Overall, these treatments are under study because they have shown promise in earlier research. While side effects can occur, they are often manageable with good medical care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these chemotherapy combinations for Mantle Cell Lymphoma because they offer unique approaches compared to standard treatments like R-CHOP or BR (bendamustine and rituximab). Arm A utilizes a combination of bendamustine, rituximab, and cytarabine, which may enhance treatment effectiveness by incorporating cytarabine, a drug known for its ability to disrupt the DNA replication of cancer cells. Arm B includes acalabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, alongside bendamustine, rituximab, and cytarabine, potentially offering a more targeted approach by interfering with cancer cell signaling. Arm C combines acalabrutinib with bendamustine and rituximab, aiming to improve outcomes by targeting the BTK pathway, which plays a crucial role in the survival of lymphoma cells. These combinations could offer more effective alternatives with potentially different side effect profiles, sparking hope for improved patient outcomes.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of various chemotherapy combinations for mantle cell lymphoma. One arm will study the combination of bendamustine, rituximab, and cytarabine, which previous studies showed led to a complete remission rate of 91%, meaning many patients showed no signs of cancer after treatment. Another arm will investigate adding acalabrutinib to bendamustine and rituximab, as research has shown this combination significantly improved the time patients lived without their cancer worsening. Acalabrutinib blocks proteins that help cancer cells grow. Early studies have demonstrated that combining these treatments is safe and effective, supporting further research in treating mantle cell lymphoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Nina D Wagner-Johnston

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed mantle cell lymphoma. Participants should be in good physical condition (ECOG score 0-2), have acceptable blood counts, liver and kidney function, and not be pregnant or breastfeeding. They must agree to use contraception and cannot have certain heart conditions, active infections, bleeding disorders, severe allergies to the drugs being tested, or be on specific medications that affect drug metabolism.

Inclusion Criteria

You are not eligible for the study if you have any of the following conditions: problems with absorbing nutrients, a history of bleeding disorders or anemia, autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura that is not under control, taking blood thinners such as warfarin within 7 days of starting the study drug, significant cerebrovascular disease or events within 6 months before starting the study drug, active infections that are not responding to treatment, severe allergic reaction to similar drugs like rituximab, bendamustine, cytarabine, or acalabrutinib.

My heart function is classified as class 2B or better, despite any history of heart issues or treatments.

I haven't taken strong or moderate CYP3A inhibitors or inducers in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three chemotherapy regimens: bendamustine, rituximab, and cytarabine; bendamustine, rituximab, cytarabine, and acalabrutinib; or bendamustine, rituximab, and acalabrutinib. Treatment cycles repeat every 28 days.

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 3 years, then every 6 months until year 10.

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Bendamustine
• Cytarabine
• Rituximab

Trial Overview The study compares three chemotherapy regimens using bendamustine, rituximab, high dose cytarabine, and acalabrutinib to see which works best for treating mantle cell lymphoma. It aims to determine if these combinations are more effective than current treatments by stopping cancer cells from growing.

How Is the Trial Designed?

Group I: Arm C (acalabrutinib, bendamustine, rituximab) Experimental Treatment 4 Interventions

Patients receive acalabrutinib PO BID on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (acalabrutinib, bendamustine, rituximab, cytarabine) Experimental Treatment 5 Interventions

Patients receive PO BID on days 1-28, bendamustine IV on days 1 and 2, and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive acalabrutinib PO BID on days 1-7 and 22-28, rituximab IV on day 1, and cytarabine IV Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Group III: Arm A (bendamustine, rituximab, cytarabine) Experimental Treatment 4 Interventions

Patients receive bendamustine IV on days 1 and 2 and rituximab IV on day 1 or 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients receive rituximab IV on day 1 and cytarabine IV every Q12 hours on days 1 and 2. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.

Acalabrutinib is already approved in United States, European Union for the following indications:

Approved in United States as Calquence for:

• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma

Approved in European Union as Calquence for:

• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Acalabrutinib demonstrated significantly higher overall response rates (ORR) and complete response (CR) rates compared to other targeted therapies for relapsed/refractory mantle cell lymphoma (MCL), indicating its efficacy in treating this condition.

The safety profile of acalabrutinib was comparable or better than that of other monotherapies, although it did show increased risks of infection and anemia compared to certain combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. Telford, C., Kabadi, SM., Abhyankar, S., et al.[2021]

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]

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]

Acalabrutinib (Calquence®) has received accelerated approval from the US FDA for treating mantle cell lymphoma, based on promising results from a phase II study.

Phase III trials are currently ongoing for acalabrutinib in mantle cell lymphoma and chronic lymphocytic leukaemia, indicating its potential for broader application in treating hematological cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: First Global Approval. Markham, A., Dhillon, S.[2018]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00690

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... The combination of the Bruton tyrosine kinase inhibitor ibrutinib with bendamustine-rituximab for first-line treatment of mantle cell lymphoma (MCL) prolonged ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40311141/

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... The combination of acalabrutinib with bendamustine-rituximab significantly improved PFS. Clinical benefit of acalabrutinib with ...

3. haematologica.org haematologica.org/article/view/haematol.2023.284896

Safety and efficacy of acalabrutinib plus bendamustine and ... Results indicate that ABR was safe and efficacious, supporting further study in patients with TN MCL. Introduction. Mantle cell lymphoma (MCL) ...

4. onclive.com onclive.com/view/acalabrutinib-plus-br-highlights-evolving-first-line-soc-for-high-risk-mantle-cell-lymphoma

Acalabrutinib Plus BR Highlights Evolving First-Line SOC ... Martin Dreyling, MD, PhD, discusses clinical trial findings with acalabrutinib plus BR in patients with high-risk mantle cell lymphoma.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02972840

NCT02972840 | A Study of BR Alone Versus in ... This study is evaluating the efficacy of acalabrutinib in combination with bendamustine and rituximab (BR) compared with placebo plus BR in subjects with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11873691/

Safety and efficacy of acalabrutinib plus bendamustine and ... This multicenter, open-label, phase Ib study (ACE-LY-106) assessed the safety and efficacy of acalabrutinib, bendamustine, and rituximab (ABR) in treatment-naï ...

7. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/calquence-acalabrutinib-plus-chemoimmunotherapy-approved-in-the-us-for-patients-with-previously-untreated-mantle-cell-lymphoma.html

CALQUENCE® (acalabrutinib) plus chemoimmunotherapy ... Based on ECHO Phase III trial results which showed more than 16 months of progression-free survival improvement vs. chemoimmunotherapy alone.