Study of Abexinostat in Patients With Relapsed or Refractory Follicular Lymphoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Drug: Abexinostat


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abexinostat<br>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<br>* Abexinostat tosylate salt is formulated into an oral tablet formulation and is available in 20 mg strength.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer