BTKi-Rituximab + Glofitamab for Lymphoma

Overseen By Preetesh Jain, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: BTKi-R, Glofitamab

Must not be taking: Warfarin, Strong CYP3A inhibitors

Disqualifiers: HIV, Hepatitis B/C, 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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding glofitamab, a type of immunotherapy, can help control high-risk mantle cell lymphoma (MCL), a type of blood cancer. Participants will first receive a combination of acalabrutinib, a BTK inhibitor, and rituximab, an antibody therapy, followed by glofitamab, to assess the combined effectiveness of these treatments. Individuals with a confirmed diagnosis of high-risk MCL who have not yet received treatment might be suitable for this study. The goal is to discover more effective ways to manage this aggressive form of lymphoma. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does mention that the use of strong CYP3A inhibitors or inducers is prohibited, and corticosteroids above a certain dose are not allowed. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Studies have shown that using acalabrutinib and rituximab together is generally safe. In one study, serious side effects were rare, including lung inflammation and COVID-19, but these were uncommon. Another study found that adding acalabrutinib to a treatment plan helped patients live longer without causing many severe problems.

For glofitamab, research has shown it is reasonably safe, especially for patients who have tried other treatments. While some side effects occur, they are usually manageable. One study reported a good response rate, suggesting that the benefits might outweigh the risks for some patients.

Overall, both treatments appear safe for most people, with serious side effects being rare. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lymphoma because they combine innovative therapies to potentially enhance patient outcomes. Acalabrutinib and Zanubrutinib are Bruton’s tyrosine kinase inhibitors (BTKi) that target cancer cell growth differently than traditional chemotherapy. When combined with Rituximab, an antibody therapy that helps the immune system identify and destroy cancer cells, they offer a unique, multi-faceted approach. Additionally, Glofitamab, used in the consolidation phase, is a novel bispecific antibody that engages both T-cells and cancer cells, aiming to boost the immune response against lymphoma. This combination approach could significantly improve effectiveness and reduce the time to response compared to standard treatments.

What evidence suggests that this trial's treatments could be effective for high-risk MCL?

Studies have shown that zanubrutinib, administered during the induction and maintenance phases of this trial, helps control the disease in patients with certain types of lymphoma. In one study, 94% of patients had their disease controlled, with 64% showing partial or complete improvement. Zanubrutinib also outperformed acalabrutinib in delaying disease progression and achieving complete responses. Meanwhile, Glofitamab, used in the consolidation phase of this trial, has shown promising results, with 52% of patients responding to the treatment and 39% achieving a complete response in cases where the lymphoma returned or did not respond to previous treatments. These findings suggest that the treatments being tested could effectively manage high-risk mantle cell lymphoma (MCL). ^{6 7 8 9 10}

Who Is on the Research Team?

Preetesh Jain, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with untreated high-risk Mantle Cell Lymphoma (MCL). Participants should be suitable for intensive chemotherapy. Specific details about inclusion and exclusion criteria are not provided, but typically these would involve age, overall health status, and the absence of certain medical conditions or treatments that could interfere with the study.

Inclusion Criteria

Life expectancy >= 12 weeks

Understanding and voluntary signing of an IRB-approved informed consent form

Bi-dimensional measurable disease using specific criteria

Exclusion Criteria

I have a history of certain medical conditions or infections.

I have had cancer before, but it was a long time ago.

My cancer has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive BTKi-Rituximab induction treatment with Acalabrutinib or Zanubrutinib

12 weeks

Consolidation

Participants receive 12 cycles of glofitamab to achieve MRD negativity

12 cycles

Maintenance

Participants receive maintenance treatment with BTKi-Rituximab and Acalabrutinib or Zanubrutinib

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Glofitamab
• Rituximab

Trial Overview The study is testing if a new treatment approach using Glofitamab after BTK inhibitor-Rituximab therapy can effectively control high-risk MCL. It's a phase 2 trial which means it focuses on effectiveness and further evaluates safety.

How Is the Trial Designed?

Group I: 3-Maintenance Experimental Treatment 2 Interventions

Phase 2 Maintenance Treatment with BTKi-R - Rituximab/Ruxience + Acalabrutinib/Zanubrutinib

Group II: 2-Consolidation Experimental Treatment 1 Intervention

Phase 2 Consolidation Treatment with Glofitamab

Group III: 1-Induction Experimental Treatment 2 Interventions

Phase 2 Induction Treatment with BTKi-R - Rituximab/Ruxience + Acalabrutinib/Zanubrutinib

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12246662/

Efficacy of zanubrutinib versus acalabrutinib for relapsed or ... These outcomes included progression-free survival, overall survival, and complete response. We found that zanubrutinib significantly improved ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e23263

Comparing real-world treatment patterns and outcomes of ... Conclusions: In this RW study, ZANU was associated with a lower discontinuation risk than ACA. Poorer survival outcomes were linked to older age ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/16/4100/537143/Zanubrutinib-is-well-tolerated-and-effective-in

Zanubrutinib is well tolerated and effective in patients with ... Of 67 efficacy-evaluable patients, 94% experienced disease control: 30% had a best response of stable disease and 64% had a partial or complete response. These ...

4. oncologynurseadvisor.com oncologynurseadvisor.com/news/zanubrutinib-acalabrutinib-chronic-leukemia-cll-treatment-risk/

Zanubrutinib Outperforms Acalabrutinib in Indirect ... Zanubrutinib demonstrated a significant advantage over acalabrutinib in progression-free survival (PFS) and complete response (CR) rates ...

5. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(24)01602-1/fulltext

MCL-509 Indirect Comparison of Efficacy of Zanubrutinib ... This STC demonstrated that zanubrutinib had significantly better PFS and OS vs acalabrutinib in the treatment of patients with R/R MCL after adjusting for a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39234862/

Safety and efficacy of acalabrutinib plus bendamustine and ... AE leading to death were pneumonitis (N=1, TN cohort), COVID-19, and cerebrospinal meningitis (N=1 each, R/R cohort). Overall response was 94.4% ...

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

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... The addition of acalabrutinib to bendamustine plus rituximab significantly improved progression-free survival (PFS) compared with placebo and ...

8. ashpublications.org ashpublications.org/blood/article/146/21/2561/546768/A-phase-2-study-of-zanubrutinib-in-combination

A phase 2 study of zanubrutinib in combination with rituximab ... Key PointsZR2 yielded a complete response rate, 2-year progression-free and overall survival rate of 65.0%, 67.1%, and 82.4% among older ...

9. nature.com nature.com/articles/s41467-025-62509-z

Frontline acalabrutinib, lenalidomide and rituximab for ... After a median follow-up of 43 months, median PFS and OS were not reached, 2-year PFS rate was 79% and 2-year OS rate was 92%. Here we show that ...

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

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 ...