What is the mechanism of action of this treatment?

The most common treatments for Mantle Cell Lymphoma (MCL) include Bruton's Tyrosine Kinase (BTK) inhibitors like acalabrutinib, which block the BTK enzyme essential for B-cell receptor signaling, thereby reducing the survival and proliferation of malignant B-cells. This is crucial for MCL patients as the disease involves uncontrolled B-cell growth. Additionally, R-CHOP therapy, which includes rituximab, targets both the cancerous B-cells and their supportive microenvironment. Rituximab, an anti-CD20 monoclonal antibody, specifically targets B-cells for destruction. Combining these therapies can enhance treatment efficacy and improve remission rates, which is vital for managing this aggressive lymphoma.

What side effects are associated with this type of intervention?

Common treatments for Mantle Cell Lymphoma (MCL) include BTK inhibitors like acalabrutinib and combination chemotherapy regimens such as R-CHOP. Acalabrutinib is generally well-tolerated but can cause side effects such as headache, diarrhea, nausea, infections, atrial fibrillation, hypertension, and bleeding. R-CHOP chemotherapy, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, is associated with side effects like neutropenia, anemia, thrombocytopenia, nausea, vomiting, hair loss, and increased risk of infections. Both treatment types require careful monitoring to manage these potential adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Mantle Cell Lymphoma (MCL), including Bruton's Tyrosine Kinase (BTK) inhibitors. Ibrutinib was the first BTK inhibitor approved for MCL in 2013, followed by Acalabrutinib in 2017. These drugs work by inhibiting the BTK enzyme, which is crucial for the growth and survival of B-cell malignancies. Other treatments for MCL include chemotherapy regimens, monoclonal antibodies like rituximab, and CAR-T cell therapies. The ongoing trial with Acalabrutinib combined with R-CHOP aims to further improve remission rates in previously untreated MCL patients.

What other types of research exist?

Promising novel alternatives to Acalabrutinib for Mantle Cell Lymphoma patients include: 1) Ibrutinib, another Bruton's Tyrosine Kinase Inhibitor, which has shown high efficacy in clinical trials. 2) Venetoclax, a BCL-2 inhibitor, which has demonstrated significant activity in relapsed/refractory MCL. 3) CAR-T cell therapy, specifically targeting CD19, which has shown durable remissions in MCL patients. These alternatives offer different mechanisms of action and have been validated in recent clinical studies.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib + R-CHOP for Mantle Cell Lymphoma

Phase 2

Waitlist Available

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologic diagnosis of MCL according to the World Health Organization classification

Men and women ≥ 18 years of age deemed eligible for treatment with full-dose R-CHOP and ASCT by the qualified investigator

Must not have

Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)

Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to end of study (up to 2 years)

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as fever or fatigue; digestive disturbances; increased risk of infections; bleeding problems due to low platelet counts; liver enzyme changes indicating potential liver damage; muscle pains or cramps; headaches; and potentially serious cardiac arrhythmias.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 or older and eligible for R-CHOP and stem cell transplant treatment.

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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.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have uncontrolled AIHA or ITP.

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I do not have a history of bleeding disorders like hemophilia.

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I have trouble swallowing pills or have a condition that affects how my body absorbs medication.

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I do not have HIV or any serious infections.

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I have not had major surgery in the last 4 weeks or have fully recovered if I did.

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I am taking warfarin or similar blood thinners.

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I need treatment with a strong medication that affects liver enzymes.

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My cancer has spread to my brain.

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I have been treated with specific inhibitors for my condition before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to end of study (up to 2 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to end of study (up to 2 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to end of study (up to 2 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Changes in scores of partient reported outcomes (PRO) as measured by EORTC QLQ-C30

Changes in scores of partient reported outcomes (PRO) as measured by FACT-Cog

Changes in scores of partient reported outcomes (PRO) as measured by FACT-Lym

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Acalabrutinib with R-CHOP chemotherapyExperimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Acalabrutinib

2020

Completed Phase 2

~2080

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Mantle Cell Lymphoma (MCL) include Bruton's Tyrosine Kinase (BTK) inhibitors like acalabrutinib, which block the BTK enzyme essential for B-cell receptor signaling, thereby reducing the survival and proliferation of malignant B-cells. This is crucial for MCL patients as the disease involves uncontrolled B-cell growth. Additionally, R-CHOP therapy, which includes rituximab, targets both the cancerous B-cells and their supportive microenvironment. Rituximab, an anti-CD20 monoclonal antibody, specifically targets B-cells for destruction. Combining these therapies can enhance treatment efficacy and improve remission rates, which is vital for managing this aggressive lymphoma.