Combination Chemotherapy + Acalabrutinib for Mantle Cell Lymphoma

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Academic and Community Cancer Research United

Must not be taking: Warfarin, Proton pump inhibitors

Disqualifiers: Peripheral neuropathy, Stroke, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 18 weeks

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for people with mantle cell lymphoma, a type of blood cancer. It tests the effects of adding acalabrutinib, a drug that blocks a key enzyme for cancer growth, to a modified version of the standard chemotherapy regimen called VR-CAP. The goal is to determine if this combination is more effective than the usual treatment for those who might eventually need a stem cell transplant. Individuals diagnosed with mantle cell lymphoma who have not received prior treatments, except for short-term symptom management, might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot participate if you need certain medications like strong CYP3A4 inhibitors/inducers 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?

In a previous study, over 1,000 patients received acalabrutinib. Common side effects included anemia (low red blood cells), neutropenia (low white blood cells), and infections. These are typical concerns but important to know.

Bortezomib has been studied in patients with mantle cell lymphoma. Research has shown it can cause similar blood-related side effects, and it is already approved for certain cases of this cancer.

Cyclophosphamide can cause serious issues like infertility and secondary cancers. However, it is a well-known drug and has been used in cancer treatments for a long time.

Cytarabine can also cause blood issues, such as anemia and neutropenia, but it is generally safe when used with other treatments for lymphoma.

Doxorubicin is another established cancer drug. It can cause tissue damage if it leaks out of the vein during administration.

Rituximab is a type of antibody treatment. Common mild side effects include fever and chills, mostly during the first infusion.

This trial is in the middle phase (Phase 2), which means some safety data is available, but more is being gathered. Each drug has known side effects, but they are typically managed in a healthcare setting. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination treatment for mantle cell lymphoma because it introduces acalabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, which targets and disrupts cancer cell growth in a different way than standard chemotherapy alone. While traditional treatments often rely on broad approaches to kill cancer cells, acalabrutinib specifically blocks signals that help cancer cells survive and multiply. Additionally, this combination leverages bortezomib, which interferes with the degradation of proteins within cancer cells, adding another layer of attack against the tumor. This multi-faceted approach aims to enhance the effectiveness of treatment and potentially improve outcomes for patients.

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

Research has shown that acalabrutinib, one of the treatments in this trial, can greatly improve outcomes for patients with mantle cell lymphoma when combined with other treatments. Specifically, it extended the time patients live without disease progression by over 16 months when added to chemoimmunotherapy. In this trial, participants will receive a combination of treatments, including acalabrutinib, bortezomib, cyclophosphamide, cytarabine, doxorubicin hydrochloride, and rituximab. Bortezomib helps patients with relapsed mantle cell lymphoma live longer. Cyclophosphamide, when combined with rituximab, increases the number of patients who respond well to treatment. High doses of cytarabine have been linked to high response rates, with many patients achieving complete remission. Rituximab, a type of targeted therapy, improves survival rates when used with chemotherapy. These treatments have shown promise in fighting mantle cell lymphoma, especially when used together. ^{2 3 6 7 8}

Who Is on the Research Team?

Stephen D Smith

Principal Investigator

Academic and Community Cancer Research United

Are You a Good Fit for This Trial?

This trial is for transplant-eligible patients aged 18-75 with mantle cell lymphoma who haven't had prior systemic treatment. They must have measurable disease, acceptable organ function, and an ECOG performance status of 0-2. Women of childbearing potential and men must agree to effective contraception during the study and afterwards.

Inclusion Criteria

Platelet count >= 100,000/mm^3 or >= 75,000/mm^3 if due to lymphomatous marrow or spleen involvement (obtained =< 30 days prior to registration)

Negative pregnancy test done within =< 14 days prior to registration for women of childbearing potential only

Absolute neutrophil count (ANC) >= 1000/mm^3 or >= 500/mm^3 if due to lymphomatous marrow or spleen involvement (obtained =< 30 days prior to registration)

Exclusion Criteria

I do not have an active infection that is getting worse or needs IV antibiotics.

I have uncontrolled AIHA or ITP.

I cannot swallow pills or have a stomach condition that affects medication absorption.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive modified VR-CAP and acalabrutinib in cycles, with treatment repeating every 21 days for up to 6 cycles

18 weeks

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 6 months

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• Bortezomib
• Cyclophosphamide
• Cytarabine
• Doxorubicin Hydrochloride
• Rituximab

Trial Overview The trial investigates a modified VR-CAP (a combination of chemotherapy drugs) plus acalabrutinib as first-line therapy compared to standard treatments. It aims to see if this new combo is more effective in treating mantle cell lymphoma before a patient undergoes a stem cell transplant.

How Is the Trial Designed?

Group I: Treatment (modified VR-CAP, acalabrutinib) Experimental Treatment 8 Interventions

CYCLES 1, 3, AND 5: Patients receive acalabrutinib PO BID on days 1-21. Patients also receive bortezomib SC on days 1, 8, and 15, rituximab (or rituximab and hyaluronidase human) IV, cyclophosphamide IV, and doxorubicin hydrochloride IV on day 1, and prednisone PO on days 1-5. CYCLES 2, 4, AND 6: Patients receive acalabrutinib PO BID on days 1-21. Patients also receive rituximab (or rituximab and hyaluronidase human) IV on day 1 and cytarabine IV on days 1-2. Treatment repeats every 21 days for up to 6 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?

Academic and Community Cancer Research United

Lead Sponsor

Trials

54

Recruited

4,900+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Zanubrutinib, a next-generation Bruton tyrosine kinase inhibitor, shows promise as a targeted therapy for mantle cell lymphoma, particularly for patients who are elderly or have comorbidities and cannot undergo standard treatments.

An ongoing Phase III study is evaluating the safety and efficacy of zanubrutinib combined with rituximab compared to bendamustine with rituximab in patients with untreated mantle cell lymphoma who are not eligible for stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. Dreyling, M., Tam, CS., Wang, M., et al.[2021]

Bruton's tyrosine kinase inhibitors, such as ibrutinib, acalabrutinib, and zanubrutinib, are effective and well-tolerated treatment options for patients with mantle cell lymphoma who have already undergone one line of therapy.

These inhibitors offer a promising alternative for patients who experience relapse or drug resistance after initial chemo-immunotherapy, highlighting the need for novel treatment strategies in this aggressive lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. Hanna, KS., Campbell, M., Husak, A., et al.[2021]

Acalabrutinib, an oral Bruton tyrosine kinase inhibitor, has shown an impressive overall response rate of 81% in patients with relapsed mantle cell lymphoma (MCL), indicating its efficacy as a treatment option.

This novel therapy is not only approved for relapsed MCL but is also being tested as a first-line treatment, highlighting its potential to improve outcomes for patients with this challenging type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib for mantle cell lymphoma. Witzig, TE., Inwards, D.[2021]

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]

In a phase II clinical trial involving 25 newly diagnosed mantle cell lymphoma (MCL) patients, an intensive chemotherapy regimen followed by autologous stem cell transplantation (auto-HSCT) resulted in a high overall response rate of 74% after induction, with a 100% response rate for those who underwent HSCT.

The long-term follow-up showed that patients receiving auto-HSCT had significantly better 5-year event-free survival (54%) and overall survival (75%) compared to those who did not receive the transplant, indicating that this treatment approach is both effective and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II clinical trial of intensive chemotherapy followed by consolidative stem cell transplant: long-term follow-up in newly diagnosed mantle cell lymphoma. Evens, AM., Winter, JN., Hou, N., et al.[2009]

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]

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. 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124105708

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 ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/216387s004lbl.pdf

Clinical Trials - accessdata.fda.gov In this pooled safety population, adverse reactions in ≥ 30% of 1029 patients were anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, ...

7. ema.europa.eu ema.europa.eu/en/documents/variation-report/calquence-h-c-005299-ii-0026-epar-assessment-report-extention-indication_en.pdf

Calquence; INN-acalabrutinib - EMA The overall B/R of Calquence for the treatment of adult patients with relapsed or refractory mantle cell lymphoma not previously treated with a ...

8. calquence.com calquence.com/

Treatment for CLL/SLL and R/R MCL | CALQUENCE ... Learn about CALQUENCE® (acalabrutinib), a treatment option for mantle cell lymphoma ... Important Safety Information About CALQUENCE® (acalabrutinib) ...