Acalabrutinib + R-CHOP for Mantle Cell Lymphoma

Recruiting at 5 trial locations

Overseen By John Kuruvilla, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: R-CHOP, Acalabrutinib

Must not be taking: BCR inhibitors, BCL-2 inhibitors

Disqualifiers: CNS involvement, Cardiovascular disease, 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: 6

Duration: 18 weeks

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining acalabrutinib (a type of targeted therapy) with R-CHOP chemotherapy for individuals with mantle cell lymphoma, a rare blood cancer. One group of participants will receive these treatments followed by a stem cell transplant, while another group will receive the treatments without the transplant. The trial seeks to determine patient response and the duration of disease stability. It is recruiting individuals newly diagnosed with mantle cell lymphoma who have not undergone other treatments, except possibly localized radiation or short-term steroid use. As a Phase 2 trial, the research focuses on assessing 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, but you cannot participate if you need certain medications like strong CYP3A4 inhibitors/inducers, warfarin, or proton pump inhibitors. 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?

Research shows that acalabrutinib, when combined with R-CHOP chemotherapy, is generally well-tolerated by patients with mantle cell lymphoma. Studies have found that acalabrutinib, a BTK inhibitor, is usually safe, with most side effects being manageable.

In some clinical trials, patients taking acalabrutinib experienced few serious side effects. Common issues included headaches or mild tiredness, typical with many treatments. Importantly, these side effects often did not require stopping treatment.

The combination of acalabrutinib with traditional chemotherapy like R-CHOP remains under study, but the safety results so far are promising. The current trial phase aims to gather more information about the treatment's safety and effectiveness, so ongoing monitoring is part of the process. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Acalabrutinib with R-CHOP for treating Mantle Cell Lymphoma because it introduces a promising new mechanism of action. Unlike the standard R-CHOP chemotherapy, Acalabrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, which targets and disrupts specific pathways that cancer cells use to grow and survive. This targeted approach could potentially enhance the effectiveness of the traditional chemotherapy regimen, offering a more comprehensive attack on the lymphoma cells. Additionally, the option for participants to undergo an autologous stem cell transplant (ASCT) after treatment in one of the cohorts might provide a longer-term benefit by helping to restore healthy blood cells more efficiently.

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

Research shows that acalabrutinib, when combined with other treatments, yields promising results for mantle cell lymphoma (MCL). Studies have found that acalabrutinib can extend the time patients live without disease progression. In this trial, participants in both Cohort A and Cohort B will receive acalabrutinib alongside standard chemotherapy such as R-CHOP. One study demonstrated significantly better outcomes for previously untreated patients when acalabrutinib was added to their regimen. This suggests that acalabrutinib, used with standard chemotherapy like R-CHOP, could be an effective option for treating MCL. The evidence supports acalabrutinib as a valuable addition to MCL treatment plans. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Adults with untreated mantle cell lymphoma eligible for R-CHOP chemotherapy and stem cell transplant can join this Canadian study. They must be able to swallow pills, understand the study risks, consent to it, and use effective birth control. Exclusions include central nervous system involvement, hypersensitivity to trial drugs, bleeding disorders, certain medication conflicts, recent major surgery or stroke, severe liver/kidney disease, other active cancers (with exceptions), significant heart issues, uncontrolled blood diseases like AIHA/ITP or live vaccinations recently.

Inclusion Criteria

My diagnosis is Mantle Cell Lymphoma (MCL) as per WHO standards.

I have a tumor that can be measured on scans, larger than 1.5 cm if in a lymph node or 1.0 cm if elsewhere.

Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty

Exclusion Criteria

You have had severe allergic reactions to the study drugs (acalabrutinib and specific components of R-CHOP), including the active ingredients or other substances in them.

My platelet count is below 50, but I can join if my low count is due to lymphoma in my bone marrow.

Total serum bilirubin >2 times the upper limit of normal (or <3 times for Gilbert's disease or documented hepatic involvement by lymphoma), AST and ALT <3 times the upper limit of normal (or <5 times for documented hepatic involvement by lymphoma)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive six cycles of R-CHOP chemotherapy together with continuous acalabrutinib

18 weeks

6 visits (in-person, every 21 days)

Response Assessment

Participants undergo response assessment with CT scan, PET/CT scan, and bone marrow biopsy

1-2 weeks

Stem Cell Mobilization and Transplantation

Responding patients proceed with stem cell mobilization, apheresis, and processing, followed by ASCT

4-6 weeks

Maintenance

Participants receive standard maintenance rituximab every 3 months

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Acalabrutinib
• R-CHOP chemotherapy

Trial Overview

This phase II trial tests acalabrutinib combined with R-CHOP chemo in patients before a stem cell transplant. Participants will take acalabrutinib twice daily with six cycles of R-CHOP and undergo scans and biopsies for response assessment. Successful responders proceed to stem cell collection followed by maintenance rituximab every three months for two years post-transplant.

How Is the Trial Designed?

Group I: Cohort B Experimental Treatment 2 Interventions

Acalabrutinib 100mg twice per day orally with standard of care R-CHOP chemotherapy by IV every 21 days for a maximum of six cycles.

Group II: Cohort A Experimental Treatment 2 Interventions

Acalabrutinib 100mg twice per day orally with standard of care R-CHOP chemotherapy by IV every 21 days for a maximum of six cycles. After 6 cycle of R-CHOP and study drug eligible participants will undergo ASCT.

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?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a phase 2 trial involving 60 younger patients with mantle cell lymphoma (MCL), the combination of cytarabine and rituximab as an induction regimen resulted in a high overall response rate of 93% after (R)-CHOP and 95% after R-DHAP, with 57% achieving complete response after R-DHAP.

The study demonstrated a median event-free survival of 83 months and a five-year overall survival rate of 75%, indicating that this treatment approach is both safe and effective, with no unexpected toxicities reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d'Etude des Lymphomes de l'Adulte. Delarue, R., Haioun, C., Ribrag, V., et al.[2022]

In a study of 20 patients with mantle cell lymphoma (MCL), the combination of rituximab and chlorambucil (R-Chl) achieved a high overall response rate of 95%, with 90% of patients reaching complete remission (CR).

The treatment resulted in a 3-year progression-free survival rate of 89% and was well-tolerated, with no serious side effects reported, making it a promising first-line option for patients with indolent disease features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. Sachanas, S., Pangalis, GA., Vassilakopoulos, TP., et al.[2019]

In a study of 87 patients with newly diagnosed mantle cell lymphoma (MCL), the treatment regimen involving R-CHOP followed by high-dose cytarabine and BEAM with stem cell rescue resulted in a 70% overall response rate, with 64% achieving complete remission.

The treatment showed manageable toxicity levels, with severe non-haematological side effects occurring in 55% of patients after BEAM, and it provided long-term failure-free survival (36% at 4 years) and overall survival (66% at 4 years), indicating potential effectiveness despite the challenges of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. van 't Veer, MB., de Jong, D., MacKenzie, M., et al.[2015]

In a study of 97 patients with mantle cell lymphoma (MCL) treated with rituximab plus bendamustine (R-B), the overall response rate was 90%, with 54% achieving a complete response, indicating that R-B is an effective first-line treatment option.

When compared to 232 patients treated with R-CHOP/R-DHAP, there were no significant differences in progression-free survival between the two treatment regimens, suggesting that R-B is as effective as R-CHOP/R-DHAP for transplant-eligible patients with MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine or high-dose cytarabine-based induction with rituximab in transplant-eligible mantle cell lymphoma. Villa, D., Hoster, E., Hermine, O., et al.[2022]

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]

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