Acalabrutinib + R-CHOP for Mantle Cell Lymphoma

Recruiting at 4 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests if taking acalabrutinib with R-CHOP chemotherapy can help patients with untreated mantle cell lymphoma achieve remission before a stem cell transplant. Acalabrutinib blocks cancer growth, and R-CHOP kills cancer cells.

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.

How is the drug Acalabrutinib + R-CHOP unique for treating mantle cell lymphoma?

The combination of Acalabrutinib with R-CHOP is unique because Acalabrutinib is a targeted therapy that specifically inhibits Bruton's tyrosine kinase (BTK), which plays a role in the growth of cancer cells, while R-CHOP is a chemotherapy regimen that attacks cancer cells in multiple ways. This combination aims to enhance treatment effectiveness by combining targeted and traditional chemotherapy approaches. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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)

Trial Timeline

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

Treatment Details

Interventions

• Acalabrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor)
• R-CHOP chemotherapy (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.

Participant Groups

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.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Dr. Brad Wouters

University Health Network, Toronto

Chief Medical Officer since 2020

MD from University of Toronto

Dr. Kevin Smith

University Health Network, Toronto

Chief Executive Officer since 2018

Professor at McMaster University and University of Toronto

Findings from Research

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England 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. [2018]

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

High-dose Ara-C and beam with autograft rescue in R-CHOP responsive mantle cell lymphoma patients. [2015]

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

Bendamustine or high-dose cytarabine-based induction with rituximab in transplant-eligible mantle cell lymphoma. [2022]

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

Combination of rituximab with chlorambucil as first line treatment in patients with mantle cell lymphoma: a highly effective regimen. [2019]