Acalabrutinib + Rituximab and CAR T-Cell Therapy for Mantle Cell Lymphoma

Overseen By Preetesh Jain, MD, PHD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: HIV, Hepatitis B/C, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use strong CYP3A inhibitors or inducers within a certain period before starting the study drug, and you cannot take warfarin or similar medications. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Acalabrutinib for treating mantle cell lymphoma?

Acalabrutinib, a type of drug called a Bruton tyrosine kinase inhibitor, has been shown to be effective for mantle cell lymphoma, with a clinical trial demonstrating an overall response rate of 81% in patients whose disease had returned after previous treatments. ^{1 2 3 4 5}

Is the combination of Acalabrutinib, Rituximab, and CAR T-Cell Therapy safe for humans?

Acalabrutinib has been shown to have a favorable safety profile in various studies, with some risks of side effects like neutropenia (low white blood cell count) and leukopenia (reduced white blood cells). It is generally well-tolerated in patients with different types of lymphoma, including mantle cell lymphoma. ^{1 4 6 7 8}

What makes the treatment with Acalabrutinib, Rituximab, and CAR T-Cell Therapy unique for mantle cell lymphoma?

This treatment is unique because it combines Acalabrutinib, a highly selective Bruton tyrosine kinase inhibitor, with Rituximab and CAR T-Cell Therapy, offering a novel approach for mantle cell lymphoma, especially for patients who have relapsed or are resistant to other treatments. Acalabrutinib is known for its minimal off-target effects, which may improve safety and adherence compared to other therapies. ^{1 2 4 5 6}

What is the purpose of this trial?

To learn if giving acalabrutinib, rituximab, and brexucabtagene autoleucel to patients with previously untreated high-risk mantle cell lymphoma (MCL) can help to control the disease.

Research Team

Preetesh Jain, MD, PHD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with newly diagnosed high-risk mantle cell lymphoma who haven't had treatment before. They must have specific genetic markers, be able to swallow pills, and have a good performance status (able to carry out daily activities). Women should not be pregnant and must use birth control. People can't join if they've had other cancers needing active treatment, certain heart or blood conditions, or are HIV positive.

Inclusion Criteria

Bi-dimensional measurable disease using the 2014 Cheson criteria

Specific serum bilirubin and Cr Clearance levels

ANC > 1,000/mm3 and platelet count >100,000/mm3

Exclusion Criteria

I have not received any live vaccines in the last 6 weeks.

Abnormal PT/INR or aPTT levels

I am currently on medication for an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive acalabrutinib and rituximab for up to 12 cycles, each cycle lasting 28 days

48 weeks

Treatment Part 2

Participants undergo leukapheresis to collect T cells, followed by CAR T-cell therapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after CAR T-cell therapy

4 weeks

Treatment Details

Interventions

• Acalabrutinib
• Brexucabtagene Autoleucel
• Rituximab

Trial Overview The study tests a combination of acalabrutinib and rituximab followed by brexucabtagene autoleucel therapy in patients with untreated high-risk mantle cell lymphoma. The goal is to see if this regimen controls the disease better than current treatments.

Participant Groups

Group I: Brexucabtagene Autoleucel (Part 2) Experimental Treatment 3 Interventions

Participants will have a procedure called leukapheresis to collect enough T cells.

Group II: Acalabrutinib and Rituximab (Part 1) Experimental Treatment 4 Interventions

Participants may receive acalabrutinib and rituximab for up to 12 cycles. Each cycle is 28 days.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Acerta Pharma, LLC

Collaborator

Trials

8

Recruited

390+

Kite, A Gilead Company

Industry Sponsor

Trials

45

Recruited

4,300+

Findings from Research

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]

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]

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]

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]

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]

In a phase 2 trial involving 124 patients with relapsed or refractory mantle cell lymphoma, acalabrutinib was associated with common treatment-related adverse events (AEs) like headache and diarrhea, but these did not lead to any treatment discontinuations.

Effective management strategies, including patient education and the use of over-the-counter medications for mild AEs, helped maintain treatment adherence and allowed for better tracking and management of nonadherence issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. Badillo, M., Nava, D., Rosa, M., et al.[2022]

Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic lymphocytic leukemia (CLL) patients, although it was associated with a higher risk of neutropenia and leukopenia in some cases.

The analysis indicated that acalabrutinib (with or without obinutuzumab) had similar efficacy in terms of progression-free survival compared to other treatments, suggesting it is a safe and effective option for CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. Davids, MS., Telford, C., Abhyankar, S., et al.[2021]

Acalabrutinib, a Bruton tyrosine kinase inhibitor, showed a 53% overall response rate in patients with relapsed/refractory marginal zone lymphoma, indicating its efficacy in this patient population.

The treatment was generally well tolerated, with a median progression-free survival of 27.4 months and a low incidence of severe adverse events, suggesting improved safety compared to other treatments like ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. Strati, P., Coleman, M., Champion, R., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Acalabrutinib: First Global Approval. [2018]

2. England pubmed.ncbi.nlm.nih.gov

The role of Bruton's tyrosine kinase inhibitors in the management of mantle cell lymphoma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A Phase III study of zanubrutinib plus rituximab versus bendamustine plus rituximab in transplant-ineligible, untreated mantle cell lymphoma. [2021]

4. United States 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Acalabrutinib for mantle cell lymphoma. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. [2021]

8. England pubmed.ncbi.nlm.nih.gov

A phase 2, multicentre, open-label trial (ACE-LY-003) of acalabrutinib in patients with relapsed or refractory marginal zone lymphoma. [2022]