What side effects are associated with this type of intervention?

Common treatments for Mantle Cell Lymphoma, particularly those involving Ibrutinib (a BTK inhibitor) and Venetoclax (a BCL-2 inhibitor), have specific side effects. Ibrutinib is associated with atrial fibrillation, hypertension, bleeding, and increased infection risk. Venetoclax can cause neutropenia, tumor lysis syndrome, and gastrointestinal issues. Both treatments are generally well-tolerated but require careful monitoring to manage these potential adverse effects.

What prior FDA approvals exist?

Ibrutinib, a Bruton tyrosine kinase (BTK) inhibitor, has been approved by the FDA for the treatment of Mantle Cell Lymphoma (MCL). Venetoclax, a BCL-2 inhibitor, is also being studied for its efficacy in MCL. These drugs target specific pathways involved in the survival and proliferation of cancer cells, offering a targeted approach to treatment. Other treatments for MCL include bendamustine plus rituximab, which has shown efficacy in relapsed or refractory cases. The combination of these targeted therapies represents a significant advancement in the management of MCL.

What other types of research exist?

Promising novel alternatives to Ibrutinib and Venetoclax for Mantle Cell Lymphoma patients include: <ol> <li>CAR T-Cell Therapy (e.g., KTE-X19) - shown to be effective in relapsed/refractory MCL.</li> <li></li> </ol> PI3K Inhibitors (e.g., Idelalisib) - demonstrated safety and activity in relapsed/refractory MCL. 3. Anti-CD79B Antibody-Drug Conjugates (e.g., Polatuzumab Vedotin) - shown activity in relapsed/refractory B-cell non-Hodgkin lymphoma, including MCL.

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BTK Inhibitor

Ibrutinib + Venetoclax for Mantle Cell Lymphoma

Phase 3

Waitlist Available

Research Sponsored by Pharmacyclics LLC.

Eligibility Criteria Checklist

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

Must have

Pathologically confirmed MCL (in tumor tissue), with documentation of either overexpression of cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5, CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR).

At least 1, but no more than 5, prior treatment regimens for MCL.

Must not have

History of HIV or active HCV or HBV.

History or current evidence of central nervous system lymphoma.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 5 years

Awards & highlights

Pivotal Trial

Summary

This trial is testing whether a combination of two drugs, ibrutinib and venetoclax, is more effective than just using ibrutinib in patients with Mantle Cell Lymphoma (MCL). Ibrutinib works by stopping cancer cells from growing, while venetoclax helps to kill them. The goal is to see if this combination can better treat MCL. Ibrutinib and venetoclax have shown promising results in treating relapsed or refractory Mantle Cell Lymphoma (MCL) and are being tested together for their potential synergistic effects.

Who is the study for?

This trial is for adults with Mantle Cell Lymphoma who've had 1-5 prior treatments but haven't responded well. They must have a confirmed diagnosis, measurable disease on scans, and good organ function. Excluded are those with allergies to study drugs, recent heart attacks or strokes, active infections like HIV/HCV/HBV, severe liver issues, or gastrointestinal problems that affect drug absorption.

What is being tested?

The SYMPATICO study tests the effectiveness of combining Ibrutinib (a known cancer drug) with Venetoclax versus Ibrutinib with a placebo in treating Mantle Cell Lymphoma. Participants will be randomly assigned to one of these two groups without knowing which one they're in.

What are the potential side effects?

Possible side effects include diarrhea, nausea, low blood cell counts leading to increased infection risk or bleeding problems; fatigue; muscle and bone pain; and potential liver dysfunction. Some may experience serious complications such as infections.

Eligibility Criteria

Inclusion Criteria

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

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My cancer is confirmed as MCL with specific markers or genetic evidence.

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I have had between 1 and 5 treatments for mantle cell lymphoma.

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My last cancer treatment did not work or my cancer got worse after it.

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I have a recent or preserved tissue sample available.

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I am able to get out of my bed or chair and move around.

Exclusion Criteria

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

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I have a history of HIV or active hepatitis B or C.

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I have or had lymphoma in my brain or spinal cord.

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I have not had major surgery in the last 4 weeks.

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I cannot take pills due to issues with my digestive system.

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I am not in another treatment study and have not taken ibrutinib or similar drugs.

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I am not in another drug study and haven't taken ibrutinib or similar drugs.

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I do not have any ongoing infections that aren’t being treated.

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I have a known bleeding disorder like von Willebrand's or hemophilia.

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I am willing and able to follow all study requirements.

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My condition is a specific type of mantle cell lymphoma.

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I finished IV treatment for a serious infection less than 14 days ago.

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I have been treated with venetoclax or similar medications before.

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I am 18 or older and have a TP53 mutation.

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I have not had a heart attack or unstable heart conditions in the last 6 months.

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My liver disease is moderate to severe.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 5 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

Complete Response (CR) (Treatment-Naive Arm)

Duration of Response (DOR) (Safety Run-in Period)

Number of Participants With Adverse Events (AEs) (Safety Run-in Period)

+6 more

Secondary study objectives

AUC of Venetoclax (Randomization Period)

AUClast if Ibrutinib (Randomization Period)

Cmax if Ibrutinib (Randomization Period)

+15 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Treatment-naiveExperimental Treatment2 Interventions

This open-label arm is designed to explore the efficacy and safety of the combination of ibrutinib and venetoclax in subjects with treatment-naive MCL. Approximately 75 subjects (of which \~25 subjects with TP53 mutation) will be enrolled and treated with ibrutinib and venetoclax.

Group II: Safety Run-in PeriodExperimental Treatment2 Interventions

Subjects are enrolled into the open-label Safety Run-in Period to evaluate the occurrence of tumor lysis syndrome (TLS) and DLTs with the concurrent administration of ibrutinib and venetoclax. Safety run-in phase for the study is closed to further enrollment as of 07-Nov-2018.

Group III: Phase 3: Ibrutinb + VenetoclaxExperimental Treatment2 Interventions

Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity

Group IV: Phase 3: Ibrutinib + PlaceboPlacebo Group2 Interventions

Subjects will be randomized to receive ibrutinib and venetoclax/placebo until clinical disease progression or unacceptable toxicity

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Venetoclax

2019

Completed Phase 3

~2240

Ibrutinib

2014

Completed Phase 4

~2060

0 / 20Eligibility 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 like Ibrutinib and BCL-2 inhibitors like Venetoclax. Ibrutinib works by inhibiting Bruton's tyrosine kinase (BTK), a protein essential for B-cell receptor signaling, which is crucial for the survival and proliferation of malignant B-cells in MCL. Venetoclax targets the B-cell lymphoma 2 (BCL-2) protein, which prevents apoptosis (programmed cell death) in cancer cells. By inhibiting BCL-2, Venetoclax promotes the death of these malignant cells. These mechanisms are significant for MCL patients as they directly target the pathways that allow cancer cells to grow and survive, offering a more effective and targeted approach to treatment.