Abexinostat + Ibrutinib for Lymphoma

No longer recruiting at 8 trial locations

Overseen By Gilles Salles, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Ibrutinib, HDAC inhibitors

Disqualifiers: Active CNS disease, Cardiovascular disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether two drugs, abexinostat (a cancer treatment) and ibrutinib, can safely work together to stop lymphoma from growing. The focus is on determining the right dosage of abexinostat to use with ibrutinib. Potential participants should have mantle cell lymphoma or diffuse large B-cell lymphoma that hasn't responded to other treatments or has returned. They must have undergone at least one previous treatment and be able to attend regular study visits. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on certain medications like strong CYP3A4 inhibitors or inducers, or drugs that cause heart rhythm issues. If you're on these, you might need to switch to a different medication before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abexinostat, when combined with ibrutinib, has been safe in earlier studies. One study tested abexinostat on individuals with non-Hodgkin lymphoma and chronic lymphocytic leukemia, and it was generally well-tolerated. Some patients experienced side effects, but these were manageable.

The FDA has already approved ibrutinib for treating certain cancers, indicating its well-established safety. Past research combining ibrutinib with other treatments found it to be mostly well-tolerated.

As this trial is in an early phase, researchers are still assessing the safety of combining abexinostat with ibrutinib. Early-phase trials aim to determine the appropriate dose and monitor for any side effects. Since this combination treatment is still under study, discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Abexinostat and Ibrutinib for treating lymphoma because it offers a novel approach compared to standard therapies like chemotherapy and targeted therapies such as Rituximab. Abexinostat is a histone deacetylase (HDAC) inhibitor that can potentially enhance the cancer-killing effects of Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor. This combination targets lymphoma cells more precisely by disrupting different pathways crucial for cancer cell survival. By working together, these drugs may improve treatment efficacy and overcome resistance seen in existing options.

What evidence suggests that abexinostat and ibrutinib could be effective for lymphoma?

Research has shown that abexinostat, a drug affecting cell growth, has potential in treating non-Hodgkin lymphoma. An earlier study demonstrated that abexinostat stopped cancer growth in some patients. Ibrutinib, which participants in this trial will also receive, has already proven effective for certain types of lymphoma. Studies suggest that combining abexinostat with ibrutinib may enhance their effectiveness in stopping cancer cell growth. Together, these treatments aim to improve outcomes for patients with lymphoma. ^{1 2 5 6 7}

Who Is on the Research Team?

Gilles Salles, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

I can follow the study's schedule and requirements.

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

Exclusion Criteria

I have been tested for Hepatitis B and do not have an active infection.

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

I am currently on blood thinners like warfarin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abexinostat and ibrutinib. Ibrutinib is administered once daily on a 28-day cycle, and abexinostat is administered orally twice daily for 7 days a week every other week on a 28-day cycle.

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abexinostat
• Ibrutinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Abexinostat and Ibrutinib Experimental Treatment 2 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.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Xynomic Pharmaceuticals, Inc.

Industry Sponsor

Trials

11

Recruited

1,200+

Citations

1. sciencedirect.com sciencedirect.com/topics/medicine-and-dentistry/abexinostat

Abexinostat - an overview Abexinostat has been included in 2 completed phase I trials for MM (ClinicalTrials.gov identifiers, NCT01149668 and NCT00562224) and for leukemias and lymphomas ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5477609/

Safety and efficacy of abexinostat, a pan-histone ... Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study.

3. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01496-4

Beyond Bruton's tyrosine kinase inhibitors in mantle cell ... This is based on promising results in the BRUIN Phase 1/2 trial (NCT03740529) with an overall response rate (ORR) of 52% and complete response ( ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-03632

Abexinostat and Ibrutinib in Treating Patients with ... Giving abexinostat and ibrutinib together may boost their effectiveness and limit or stop the growth of cancer cells in patients with diffuse large B-cell ...

5. medsci.org medsci.org/v16p0424.pdf

Histone Deacetylases (HDACs) Guided Novel Therapies ... In cellular studies, SAHA effectively inhibited the proliferation of human mantle cell lymphoma cells, human T-cell lymphotropic virus type I ( ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12123727/

Safety, pharmacokinetics, and efficacy of abexinostat, an ... Abexinostat, an novel pan-histone deacetylase inhibitor, induces tumor apoptosis and demonstrates therapeutic potential in B cell non-Hodgkin ...

7. hemonc.org hemonc.org/wiki/Abexinostat_(PCI-24781)

Abexinostat (PCI-24781) Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: Results of a phase 2 study.