Acalabrutinib + Chemotherapy for Mantle Cell Lymphoma

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: BTK inhibitors, Strong CYP3A4 inhibitors, Warfarin, Proton pump inhibitors

Disqualifiers: Chemotherapy, Brain lymphoma, Cardiovascular, 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: 1

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of a new combination of treatments for individuals with untreated mantle cell lymphoma, a type of blood cancer. The treatment includes acalabrutinib (a targeted therapy), bendamustine, and rituximab, followed by acalabrutinib, cytarabine, and rituximab. Researchers hope this approach will improve the complete response rate before a stem cell transplant. Individuals diagnosed with mantle cell lymphoma who are eligible for a stem cell transplant might be suitable candidates for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like strong CYP3A4 inhibitors/inducers, warfarin, or proton pump inhibitors. It's best to discuss your current medications with the trial team.

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

Research has shown that the combination of acalabrutinib, bendamustine, rituximab, and cytarabine is generally well-tolerated by patients with mantle cell lymphoma (MCL). One study found this treatment safe for patients who had not received prior treatment. Most side effects, such as low blood cell counts and infections, were expected and manageable, as they are common with these cancer treatments.

Another study examined the addition of acalabrutinib to bendamustine and rituximab and found it safe and effective. Patients responded well without any unexpected safety issues. Overall, these studies suggest that the treatment is safe for people with MCL, although side effects may occur, as with any cancer therapy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment combining acalabrutinib, bendamustine, and rituximab for mantle cell lymphoma because it introduces a novel mechanism of action with acalabrutinib. Unlike traditional chemotherapy, which targets rapidly dividing cells broadly, acalabrutinib specifically blocks the BTK enzyme, a key player in cancer cell survival and proliferation. This targeted approach aims to improve effectiveness while potentially reducing side effects. Additionally, the use of cytarabine and growth factors in later cycles is designed to enhance the treatment's impact and support patient recovery, offering a comprehensive and potentially more effective regimen.

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

In this trial, participants will receive a combination of acalabrutinib with chemoimmunotherapy. Research has shown that this combination helps patients with mantle cell lymphoma (MCL) live longer without disease progression compared to chemoimmunotherapy alone. The trial will test the combination of bendamustine and rituximab, which studies have found to be highly effective for MCL, providing long-term disease control. Additionally, high-dose cytarabine will be included, as it has led to better outcomes, with many patients remaining in remission for extended periods. Adding rituximab to chemotherapy has been proven to increase overall survival in patients with MCL. These findings suggest that this combined treatment approach holds promise for effectively treating MCL. ^{6 7 8 9 10}

Who Is on the Research Team?

Brad S. Kahl

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with untreated mantle cell lymphoma who are eligible for stem cell transplantation. Participants must have adequate organ and bone marrow function, no history of significant bleeding disorders or major surgery within the last month, and not be on certain medications like strong CYP3A4 inhibitors or proton pump inhibitors. Pregnant or breastfeeding women cannot join.

Inclusion Criteria

- Absolute neutrophil count ≥ 1,000/mcL unless, in the opinion of the treating physician, neutropenia is due to splenomegaly or bone marrow involvement

Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

I am eligible for a stem cell transplant using my own cells.

Exclusion Criteria

I have not had a live virus vaccine in the last 28 days.

I am allergic to certain medications used in this study.

I need medication that strongly affects liver enzyme levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acalabrutinib plus bendamustine and rituximab for Cycles 1-3, followed by acalabrutinib plus cytarabine and rituximab for Cycles 4-6

6 months

Cycles 1-3: Bendamustine on Days 1 and 2, Rituximab on Day 1, Acalabrutinib BID on Days 1-28; Cycles 4-6: Rituximab on Day 1, Cytarabine every 12 hours on Days 1 and 2, Acalabrutinib BID on Days 1-7 and 22-28

Leukapheresis

Patients undergo leukapheresis after completion of Cycle 6

Up to 5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Long-term Follow-up

Participants are monitored for progression-free survival and overall survival

Through 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Bendamustine
• Cytarabine
• Rituximab

Trial Overview The study tests acalabrutinib combined with bendamustine/rituximab followed by cytarabine/rituximab in patients with mantle cell lymphoma. The goal is to see if this regimen before a stem cell transplant can improve response rates and outcomes compared to current treatments.

How Is the Trial Designed?

Group I: Bendamustine/Rituximab/Acalabrutinib/Cytarabine Experimental Treatment 8 Interventions

* Patients will receive (6) 28 day cycles * Cycles 1-3 will consist of bendamustine on Days 1 and 2, rituximab on Day 1, and acalabrutinib twice per day (BID) on Days 1 through 28. * Cycles 4-6 will consist of rituximab on Day 1, cytarabine every 12 hours on Days 1 and 2, acalabrutinib BID on Days 1 through 7 and 22 through 28 (one week on, two weeks off, one week on), and growth factors as per institutional standard * After Cycle 6, patients will undergo leukapheresis

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?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Acerta Pharma BV

Industry Sponsor

Trials

46

Recruited

5,900+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7744/528340/Real-World-Effectiveness-and-Safety-Outcomes-of

Real-World Effectiveness and Safety Outcomes of ... Results: Among 181 pts with MCL treated with acala, 127 were treated in the R/R setting (study cohort) (acala monotherapy: 94 pts; combination ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10772531/

Final results and overall survival data from a phase II study ... The final results of this study demonstrated that efficacy and safety of acalabrutinib were maintained compared with data from a previous analysis (median ...

3. 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.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6777435/

Evaluating Acalabrutinib In The Treatment Of Mantle Cell ... The median duration of response was 17.5 months with PFS and OS rates of 31% and 47%, respectively, at 2 years and are the highest reported for a single agent ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02213926

NCT02213926 | An Open-label, Phase 2 Study of ACP-196 ... The purpose of this study is to characterize the safety and efficacy profile of ACP-196 (acalabrutinib) in subjects with relapsed or refractory Mantle Cell ...

6. 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 ...

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

Acalabrutinib Plus Bendamustine-Rituximab in Untreated ... Should acalabrutinib be added to bendamustine plus rituximab as frontline therapy in older patients with mantle cell lymphoma (MCL)?. Knowledge ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37183115/

Bendamustine/Rituximab Plus Cytarabine ... - PubMed The pilot studies provided preliminary safety data ... Keywords: Acalabrutinib; High-dose cytarabine; Mantle cell lymphoma; Minimal residual disease; Progression- ...

9. 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) ...

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265023001313

Original Study Bendamustine/Rituximab Plus Cytarabine ... Safety and efficacy of acalabrutinib plus bendamustine and rituximab in patients with treatment-naïve or relapsed/refractory mantle cell lymphoma: phase Ib ...