What side effects are associated with this type of intervention?

The combination of Acalabrutinib, Lenalidomide, and Rituximab for treating Mantle Cell Lymphoma can lead to several side effects. Acalabrutinib, a BTK inhibitor, may cause headaches, diarrhea, and an increased risk of infections. Lenalidomide, an immunomodulatory agent, is associated with neutropenia, higher infection risk, and thromboembolic events. Rituximab, an anti-CD20 monoclonal antibody, can result in infusion reactions, infections, and cytopenias. Patients receiving this combination therapy should be closely monitored for these potential side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for Mantle Cell Lymphoma (MCL) that are similar to the combination of Acalabrutinib, Lenalidomide, and Rituximab. Acalabrutinib, a BTK inhibitor, was approved for MCL in 2017. Lenalidomide, an immunomodulatory agent, received FDA approval for MCL in 2013. Rituximab, an anti-CD20 monoclonal antibody, has been a cornerstone in MCL treatment since its approval in 1997. These approvals highlight the efficacy of targeting B-cell pathways and modulating the immune response in MCL therapy.

What other types of research exist?

Promising novel alternatives for Mantle Cell Lymphoma treatment in 2024 include: 1) Other BTK inhibitors like Ibrutinib, which has shown durable single-agent activity in MCL. 2) Emerging agents targeting the NF-kB pathway, such as NIK inhibitors, for patients refractory to BCR pathway inhibitors. 3) Novel immunomodulatory agents like CELMoDs (e.g., iberdomide). 4) Anti-BCMA therapies, including bispecific T cell engagers (BiTEs) and chimeric antigen receptor (CAR) T cell therapies targeting BCMA. These alternatives offer new mechanisms of action and potential efficacy for MCL patients.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Acalabrutinib + Lenalidomide + Rituximab for Mantle Cell Lymphoma

Phase 2

Waitlist Available

Led By Jia Ruan, M.D., Ph.D.

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

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

Must have

All subjects must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS®

ECOG performance status ≤ 2

Must not have

Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass

Patient at high risk for deep vein thrombosis not willing to take DVT prophylaxis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for patients with untreated mantle cell lymphoma. The treatment aims to stop cancer growth, help the immune system fight the cancer, and directly target and kill the cancer cells.

Who is the study for?

This trial is for adults with untreated mantle cell lymphoma who need treatment, have good liver and kidney function, can follow the study schedule, and agree to use birth control. People with certain heart conditions, active infections like HIV or hepatitis B/C, recent major surgery, other cancers within 5 years (except some skin or localized cancers), or those on specific medications are excluded.

What is being tested?

The trial tests a combination of acalabrutinib, lenalidomide and rituximab (ALR) in patients with untreated mantle cell lymphoma over an induction phase of 12 cycles followed by maintenance therapy until disease progression or unacceptable side effects occur. The effectiveness and safety of this regimen will be monitored throughout the study.

What are the potential side effects?

Possible side effects include reactions to infusions such as fever or chills; blood disorders like low white cells increasing infection risk; digestive issues; fatigue; allergic reactions; potential bleeding problems due to aspirin required for anticoagulation; and risks associated with long-term use of lenalidomide.

Eligibility Criteria

Inclusion Criteria

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

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I am registered and can follow the Revlimid REMS program.

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I can take care of myself and do some daily activities.

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I have not had any drug treatments for lymphoma.

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I am 18 years old or older.

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My tumor is larger than 1.5 cm or my spleen is affected.

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My diagnosis is mantle cell lymphoma confirmed by tissue analysis.

Exclusion Criteria

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

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I have a condition that affects how my body absorbs food.

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I am at high risk for blood clots and refuse to take preventive medication.

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I do not have a bleeding disorder like hemophilia.

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My cancer has blastoid features.

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I do not have serious heart problems like recent heart attacks or uncontrolled heart rhythm issues.

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I have not had major surgery in the last 28 days or have fully recovered from it.

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My cancer has spread to my brain.

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I have been treated with a BTK inhibitor before.

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I do not have an ongoing serious infection that isn't getting better with treatment.

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I have uncontrolled AIHA or ITP.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Peripheral blood minimum residual disease (MRD)-negative complete response (CR) rate of the combination of acalabrutinib + lenalidomide + rituximab at the conclusion of 12 cycles of induction therapy

Secondary study objectives

Complete response rate

Overall response rate

Overall survival

+3 more

Side effects data

From 2020 Phase 2 trial • 177 Patients • NCT04346199

Headache

Septic shock

Ischaemic stroke

Chronic obstructive pulmonary disease

100%

80%

60%

40%

20%

Study treatment Arm

BSC Alone

Acalabrutinib + BSC

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: ALR in CombinationExperimental Treatment3 Interventions

Acalabrutinib, lenalidomide, and rituximab in combination

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lenalidomide

2005

Completed Phase 3

~2240

Rituximab

1999

Completed Phase 4

~2990

Acalabrutinib

2020

Completed Phase 2

~2080

0 / 16Eligibility 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

Mantle Cell Lymphoma (MCL) treatments often include BTK inhibitors, immunomodulatory agents, and anti-CD20 monoclonal antibodies. BTK inhibitors, such as acalabrutinib, block Bruton's tyrosine kinase, a protein essential for B-cell receptor signaling, thereby inhibiting the growth and survival of malignant B-cells. Immunomodulatory agents like lenalidomide enhance the immune system's ability to attack cancer cells and inhibit angiogenesis, which is crucial for tumor growth. Anti-CD20 monoclonal antibodies, such as rituximab, target the CD20 protein on the surface of B-cells, leading to their destruction. These mechanisms are vital for MCL patients as they directly target the malignant B-cells, improve immune response, and reduce tumor proliferation, offering a multi-faceted approach to treatment.