What side effects are associated with this type of intervention?

Common treatments for Mantle Cell Lymphoma include chemotherapy regimens such as bendamustine plus rituximab, and targeted therapies like ibrutinib. Known side effects of these treatments can include myelosuppression (leading to anemia, neutropenia, and thrombocytopenia), gastrointestinal issues (nausea, vomiting, diarrhea), fatigue, and increased risk of infections. For treatments similar to Abexinostat, which is a Histone Deacetylase Inhibitor, side effects often include fatigue, gastrointestinal disturbances, hematologic toxicities (such as thrombocytopenia and neutropenia), and potential liver enzyme abnormalities.

What prior FDA approvals exist?

FDA-approved treatments for Mantle Cell Lymphoma (MCL) include various targeted therapies and chemotherapeutic agents. One notable class of drugs similar to Abexinostat (a Histone Deacetylase Inhibitor) is the proteasome inhibitors, such as bortezomib. Additionally, Bruton tyrosine kinase (BTK) inhibitors like ibrutinib have been approved for MCL. Other treatments include CAR-T cell therapies, such as brexucabtagene autoleucel, which target CD19. These therapies have shown efficacy in relapsed or refractory MCL, providing multiple options for patients.

What other types of research exist?

Promising novel alternatives to Abexinostat for Mantle Cell Lymphoma patients include: 1) Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, which has shown significant efficacy in MCL. 2) Venetoclax, a BCL-2 inhibitor, which is being studied in combination with other agents for MCL. 3) CAR T-cell therapies, such as KTE-X19 (Tecartus), which have shown promising results in relapsed/refractory MCL. 4) Bispecific antibodies, like glofitamab, which are being investigated for their potential in MCL treatment.

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Histone Deacetylase Inhibitor

Abexinostat + Ibrutinib for Lymphoma

Phase 1

Waitlist Available

Led By Gottfried von Keudell, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Allogeneic stem cell transplant recipients be greater than 6 months post transplant, not on immunosuppression for prevention of graft versus host disease for >3 months and without active graft versus host disease

For patients with documented bone marrow involvement of underlying MCL or DLBCL at time of study enrollment, Hgb must be ≥ 8.0 g/dL

Must not have

Patients previously treated with ibrutinib or HDAC inhibitor

Patient is currently receiving warfarin or other Vitamin K antagonist. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed. Refer to Section 9.5 for Concomitant medication

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests if combining abexinostat and ibrutinib can safely stop cancer growth in patients by blocking enzymes and proteins that help cancer cells grow and survive. Ibrutinib is a medication approved for treating various cancers.

Who is the study for?

Adults with certain types of lymphoma (Diffuse Large B-cell or Mantle Cell) who've had at least one prior treatment and are not eligible for a stem cell transplant. They must have measurable cancer, be in relatively good health, able to take oral meds, and agree to birth control measures. Excludes those with recent major surgery, active infections like hepatitis C/B, other cancers within 5 years except specific non-threatening types, uncontrolled heart conditions, or if they've been treated with similar drugs before.

What is being tested?

The trial is testing the safety of different doses of abexinostat combined with ibrutinib to see if this combination can halt the growth of Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma. The goal is to determine the best dose that works effectively without causing too many side effects.

What are the potential side effects?

Potential side effects include reactions related to immune system suppression such as increased risk of infection, liver problems indicated by changes in blood tests for liver function, bleeding issues due to low platelet counts or other clotting disorders. There may also be gastrointestinal disturbances affecting how well patients absorb their medications.

Eligibility Criteria

Inclusion Criteria

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

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I had a stem cell transplant over 6 months ago, am not on recent immunosuppression, and don't have active graft versus host disease.

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My hemoglobin level is at least 8.0 g/dL despite having bone marrow cancer involvement.

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I have diffuse large B-cell lymphoma and have tried at least one treatment or cannot undergo a stem cell transplant.

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My potassium levels are normal, with or without supplements.

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My blood counts and organ functions are within the required ranges for the study.

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My platelet count is above 75,000 without transfusions, despite my bone marrow cancer.

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I can swallow and keep down pills.

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I have been diagnosed with either mantle cell lymphoma or diffuse large B cell lymphoma.

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I can take care of myself and perform daily activities.

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I have mantle cell lymphoma and have undergone at least one treatment.

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My lymphoma is a specific type that does not originate from the germinal center.

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I have had a stem cell transplant and no longer need blood transfusions.

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I am 18 years old or older.

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My lymphoma is a specific type that does not originate from the germinal center.

Exclusion Criteria

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

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I have been treated with ibrutinib or an HDAC inhibitor before.

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I am currently on blood thinners like warfarin.

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I still experience side effects from cancer treatment, except for hair loss.

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I have or had hepatitis B or C.

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I have a GI condition that could affect how my body absorbs medication.

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I have severe liver disease.

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My cancer has spread to my brain or its coverings.

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I am currently using other cancer treatment drugs.

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I am not pregnant or breastfeeding.

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I am currently experiencing symptoms of graft versus host disease.

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I have another active cancer besides the one being treated.

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I have HIV or an uncontrolled infection.

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I need ongoing treatment with certain strong medications that cannot be stopped or changed before starting the study drug.

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I do not have serious heart problems or recent heart attacks.

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I have a bleeding disorder such as von Willebrand's disease or hemophilia.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

the MTD of abexinostat when combined with ibrutinib

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: Abexinostat and IbrutinibExperimental Treatment2 Interventions

The investigational agents to be used in this study are ibrutinib and abexinostat. Ibrutinib will be administered once daily on a 28-day cycle. Abexinostat will be administered orally twice daily (approximately 4-6 hours apart) for 7 days a week given every other week on a 28-day cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Abexinostat

2018

Completed Phase 1

~40

Ibrutinib

2014

Completed Phase 4

~2060

0 / 29Eligibility 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 target specific cellular mechanisms to halt cancer progression. Histone Deacetylase Inhibitors (HDACi) like Abexinostat work by altering gene expression through chromatin remodeling, which can induce cancer cell death and enhance the effects of other therapies. Immunomodulatory drugs (IMiDs) such as lenalidomide modulate the immune system to attack cancer cells. Proteasome inhibitors like bortezomib disrupt protein degradation, leading to cancer cell apoptosis. Monoclonal antibodies such as rituximab target specific antigens on cancer cells, marking them for destruction by the immune system. These treatments are crucial for MCL patients as they offer multiple avenues to combat the disease, often in combination, to improve efficacy and overcome resistance.

PI3K/mTOR inhibition markedly potentiates HDAC inhibitor activity in NHL cells through BIM- and MCL-1-dependent mechanisms in vitro and in vivo.