Clinical trial NCT03600441: Study of Abexinostat in Patients With Relapsed or Refractory Follicular Lymphoma
Official title: Open-label, Single-Arm, Phase 2 Study of Oral HDAC-inhibitor Abexinostat in Patients With Relapsed or Refractory Follicular Lymphoma (FORERUNNER)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Follicular Lymphoma
Keywords: cancer
Lead sponsor: Xynomic Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-07-26
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Clinical effect of abexinostat
timeFrame: Time frame up to 100 months
Secondary outcomes:
measure: Duration of response
timeFrame: At the end of cycle 2 (each cycle is 28 days) and through study completion, assessed up to 100 months.
measure: Progression free survival
timeFrame: 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
measure: Clinical Benefit
timeFrame: At the end of cycle 2 (each cycle is 28 days) and through study completion, assessed up to 100 months.
measure: Overall survival
timeFrame: 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
measure: Duration of response
timeFrame: 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
measure: Incidence of adverse events
timeFrame: 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
measure: Incidence of serious adverse events
timeFrame: 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
measure: Incidence of non-serious adverse events
timeFrame: 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
measure: Change in the interval corrected for heart rate (QTc) interval
timeFrame: 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
Other outcomes:
Locations:
city: Park Ridge
country: United States
facility: Advocate Medical Group - Park Ridge, Luther Lane - Oncology
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute - St. Matthews Campus
state: Kentucky
city: Lake Success
country: United States
facility: Clinical Research Alliance Inc
state: New York
city: New York
country: United States
facility: Manhattan Hematology Oncology Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: Bone Marrow Transplant Hematology Oncology Associates
state: Pennsylvania
city: Arlington
country: United States
facility: Arlington Cancer Center
state: Texas
city: Temple
country: United States
facility: Central Texas Veterans Health Care System - NAVREF
state: Texas
city: Olympia
country: United States
facility: Vista Oncology Inc. PS
state: Washington
city: Perpignan
country: France
facility: Centre Hospitalier de Perpignan
state: Pyrénées-Orientales
city: Donostia-San Sebastián
country: Spain
facility: Hospital Universitario de Donostia
state: Guipúzcoa
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Córdoba
country: Spain
facility: C.H. Regional Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Connie W Batlevi, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: