Study of Abexinostat in Patients With Relapsed or Refractory Follicular Lymphoma (FORERUNNER)

Open-label, Single-Arm, Phase 2 Study of Oral HDAC-inhibitor Abexinostat in Patients With Relapsed or Refractory Follicular Lymphoma (FORERUNNER)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Follicular Lymphoma
• Intervention / Treatment: Drug: Abexinostat

Detailed Description

Patients will be evaluated for objective response, Duration of Response (DOR), Progression Free Survival (PFS), Clinical Benefit Rate (CBR), Overall survival (OS), safety and tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and changes in health related quality of life. Patients may receive treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent. An independent data safety monitoring committee (iDMC) will evaluate the data pertaining to the futility and decide whether the study should stop or continue to the second stage. If the study continues to the second stage, a total of 139 patients will be studied.

• Study Type: Interventional
• Enrollment (Estimated): 139
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Pyrénées-Orientales
    • Perpignan, Pyrénées-Orientales, France, 66046
      • Centre Hospitalier de Perpignan
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Barcelona, Spain, 28229
    • Hospital Del Mar
  • Córdoba, Spain, 14004
    • C.H. Regional Reina Sofia
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Guipúzcoa
    • Donostia-San Sebastián, Guipúzcoa, Spain, 20014
      • Hospital Universitario de Donostia
• United States
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Advocate Medical Group - Park Ridge, Luther Lane - Oncology
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute - St. Matthews Campus
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance Inc
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • Manhattan Hematology Oncology Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224-2156
      • Bone Marrow Transplant Hematology Oncology Associates
  • Texas
    • Arlington, Texas, United States, 76012
      • Arlington Cancer Center
    • Temple, Texas, United States, 76504
      • Central Texas Veterans Health Care System - NAVREF
  • Washington
    • Olympia, Washington, United States, 98506
      • Vista Oncology Inc. PS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is able to understand and voluntarily sign an informed consent document before any study related assessments/procedures are conducted.
• Has histologically confirmed Grade 1, 2, or 3a follicular lymphoma.
• Has follicular lymphoma that has relapsed after (progressed after 6 months from the start of therapy) or is refractory to the last line of therapy (no response or progression within 6 months from the start of therapy) and needs treatment (must have at least 1 lymph node or extranodal lymphoid malignancy radiologically measuring ≥ 3 cm in its longest diameter).

• Female patients must fulfil the following criteria:

  a. Be of non-childbearing potential, defined as follows: i. Postmenopausal (ie, ≥ 1 year without any menses) prior to Screening, or ii. Documented surgically sterile (≥ 1 month prior to Screening)

• Male patients must agree not to donate sperm starting from the time of Screening, throughout the study, and until after 90 days following the last dose.

• Use highly effective forms of birth control (women of childbearing potential only), which include the following:

  i. Consistent and correct use of established oral contraception ii. Established intrauterine device or intrauterine system iii. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

• Female patients must agree not to breastfeed starting from the time of Screening, throughout the study, and until after 90 days following the last dose.
• Male patients and their female spouse/partners who are of childbearing potential must use highly effective contraception methods consisting of 2 forms of birth control (at least 1 of which must be a barrier method) from the time of Screening, throughout the study, and until after 90 days following the last dose.
• Male patients must agree not to donate sperm starting from the time of Screening, throughout the study, and until after 90 days following the last dose.

Exclusion Criteria:

• Has diagnosis of Grade 3b follicular lymphoma, or transformation to diffuse large B-cell lymphoma
• Has a history of central nervous system lymphoma (either primary or secondary).
• Has had prior treatment with abexinostat.
• Has had allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before enrollment
• Has any types of cardiac impairment at the time of enrollment
• Has received any investigational medication within 30 days or 5 half-lives prior to Day 1, whichever is longer
• Has prior history of malignancies, other than follicular lymphoma, unless the patient has been free of the disease for ≥ 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abexinostat; 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).	Drug: Abexinostat; Abexinostat tosylate salt is formulated into an oral tablet formulation and is available in 20 mg strength.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical effect of abexinostat	Complete response (CR) or partial response (PR) according to the Lugano 2014 criteria as determined by an Independent Review Committee (IRC).	Time frame up to 100 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	Duration of response defined as the time from first documented evidence of CR or PR until disease progression or death from any cause among patients who achieve an objective response, according to the Lugano 2014 criteria as determined by an IRC.	At the end of cycle 2 (each cycle is 28 days) and through study completion, assessed up to 100 months.
Progression free survival	Defined as the time from the start of treatment until disease progression or death assessed using the Lugano 2014 criteria as determined by an IRC.	From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Clinical Benefit	Defined as the best from CR, PR, or stable disease (SD) according to the Lugano 2014 criteria as determined by an IRC.	At the end of cycle 2 (each cycle is 28 days) and through study completion, assessed up to 100 months.
Overall survival	Defined as the time from the start of treatment until death from any cause or last contact.	From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Duration of response	Defined as the time from first documented evidence of CR or PR from any cause among patients who achieve an objective response, according to the RECIL 2017 as determined by an IRC. Duration of response will be evaluated once more using the RECIL 2017 with the inclusion of Minor Response (MR) lasting ≥ 6 months.	At the end of cycle 2 (each cycle is 28 days) or from date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Incidence of adverse events	Safety as measured by the incidence of adverse events	At the end of cycle 2 (each cycle is 28 days) or from date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Incidence of serious adverse events	Safety as measured by the serious of adverse events (SAE)	At the end of cycle 2 (each cycle is 28 days) or from date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Incidence of non-serious adverse events	Safety as measured by the non-serious of adverse events	At the end of cycle 2 (each cycle is 28 days) or from date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months
Change in the interval corrected for heart rate (QTc) interval	Change from baseline in the QTc interval.	At the end of cycle 2 (each cycle is 28 days) or from date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 100 months

Collaborators and Investigators

• Sponsor: Xynomic Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Connie W Batlevi, MD,PhD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• FDA Safety Alerts

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 23, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: cancer
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Histone Deacetylase Inhibitors; Abexinostat
• Other Study ID Numbers: XYN-601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No