Abexinostat for Follicular Lymphoma

(FORERUNNER Trial)

Recruiting at 14 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Xynomic Pharmaceuticals, Inc.

Disqualifiers: Grade 3b lymphoma, CNS lymphoma, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 28

Duration: 28-day cycles, up to 100 months

139 Participants Needed

Trial Summary

What is the purpose of this trial?

This study in patients with relapsed/refractory follicular lymphoma who have undergone at least 3 lines of therapy. Patients will receive abexinostat 80 mg (4 × 20 mg tablets) twice a day (BID) in a "one week on, one week off" schedule.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What is known about the safety of Abexinostat in humans?

Abexinostat has been studied in patients with various types of lymphoma and leukemia, showing manageable side effects. Common side effects include low blood platelet counts (thrombocytopenia), low white blood cell counts (neutropenia), and anemia, but these were generally reversible. Serious side effects were reported in some patients, but the treatment was considered to have manageable toxicity overall. ^{1 2 3 4 5}

How is the drug Abexinostat unique in treating follicular lymphoma?

Abexinostat is unique because it is an oral histone deacetylase inhibitor (a type of drug that affects gene expression) that shows promising results in follicular lymphoma, with a higher response rate compared to other B-cell malignancies. Its twice-daily dosing schedule allows for continuous exposure, which may enhance its effectiveness in killing tumor cells. ^{1 2 6 7 8}

Research Team

Connie Batlevi, MD, PhD, MS

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients with Grade 1, 2, or 3a follicular lymphoma that's come back or didn't respond to at least three prior treatments. Participants must use effective birth control and not breastfeed or donate sperm during the study and for 90 days after. Exclusions include central nervous system lymphoma history, previous abexinostat treatment, cardiac issues, recent investigational drugs, other cancers within three years (except skin cancer), Grade 3b lymphoma or large B-cell transformation.

Inclusion Criteria

I am a woman who cannot become pregnant because I am postmenopausal or have been surgically sterilized.

My lymphoma is confirmed as Grade 1, 2, or 3a.

I agree not to donate sperm from the start of the study until 90 days after the last dose.

Exclusion Criteria

Has received any investigational medication within 30 days or 5 half-lives prior to Day 1, whichever is longer

I have been cancer-free from other types of cancer for over 3 years.

I have a heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abexinostat 80 mg BID in a 'one week on, one week off' schedule

28-day cycles, up to 100 months

Visits every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 months

Treatment Details

Interventions

• Abexinostat

Trial Overview The trial tests Abexinostat in patients with relapsed/refractory follicular lymphoma following multiple therapies. Patients will take Abexinostat orally twice daily on a schedule of one week on followed by one week off.

Participant Groups

Group I: Abexinostat Experimental Treatment 1 Intervention

Abexinostat tablets will be administered orally at 80 mg (4 × 20 mg tablets) BID (twice a day) 4 hours apart for 7 days in a "one week on, one week off" schedule (on Days 1 to 7 and Days 15 to 21 of each 28-day cycle).

Who Is Running the Clinical Trial?

Xynomic Pharmaceuticals, Inc.

Lead Sponsor

Trials

11

Recruited

1,200+

Findings from Research

The chimeric anti-CD20 monoclonal antibody IBI301 was well tolerated in nine Chinese patients with CD20(+) B-cell non-Hodgkin's lymphoma, with no severe adverse events or dose-limiting toxicities reported during the study.

IBI301 effectively eliminated peripheral CD20-expressing B cells in all patients, indicating its potential efficacy in targeting B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. Jiang, B., Qi, JY., Sun, MY., et al.[2020]

In a phase II trial involving 29 patients with untreated follicular lymphoma, rituximab combined with fludarabine and mitoxantrone achieved a high overall response rate of 100% and a complete remission rate of 66%, with notably higher remission rates in female patients.

Pharmacokinetic analysis revealed significant variability in rituximab serum concentrations, which correlated with treatment outcomes; specifically, higher serum levels were linked to better remission quality and longer progression-free survival, suggesting that dosing may need to be tailored based on patient characteristics like gender and bone marrow infiltration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Jäger, U., Fridrik, M., Zeitlinger, M., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase 1 study of the oral histone deacetylase inhibitor abexinostat in patients with Hodgkin lymphoma, non-Hodgkin lymphoma, or chronic lymphocytic leukaemia. [2018]

2. Italy pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study. [2019]

3. China pubmed.ncbi.nlm.nih.gov

[Tolerance and pharmacodynamics phase Ⅰ clinical trial study of chimeric anti-CD20 monoclonal antibody IBI301 in Chinese patients with CD20-positive non-Hodgkin's lymphoma]. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Vorinostat for treatment of cutaneous manifestations of advanced primary cutaneous T-cell lymphoma. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A multicenter phase 1 study of plerixafor and rituximab in patients with chronic lymphocytic leukemia. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Current treatment of follicular non-Hodgkin's lymphoma. [2019]