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A Clinical Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Abexinostat in Chinese Patients

Phase 1
Active, not recruiting
Conditions
Non Hodgkin Lymphoma
Interventions
Registration Number
NCT04024696
Lead Sponsor
Xynomic Pharmaceuticals, Inc.
Brief Summary

This is an open-label, non-randomized clinical study to evaluate the pharmacokinetic (PK) profiles, safety, tolerability and preliminary efficacy of oral abexinostat monotherapy in patients with non-Hodgkin's lymphoma who have failed standard of care, and thereby to determine the pharmacokinetic (PK) parameters, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of the oral monotherapy of abexinostat.

Detailed Description

This is an open-label, non-randomized clinical study to evaluate the pharmacokinetic (PK) profiles, safety, tolerability and preliminary efficacy of oral abexinostat monotherapy in patients with non-Hodgkin's lymphoma who have failed standard of care, and thereby to determine the pharmacokinetic (PK) parameters, the maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of the oral monotherapy of abexinostat.

Three (3) dose groups are pre-set to include 40 mg BID, 60 mg BID and 80 mg BID,respectively.The pre-set dose group is subject to change during the study and the actual dosage increment is determined by the Data safety Monitoring Committee (DSMC). A total of 12-16 subjects in the RP2D dose group will be required to accept PK blood sampling for the analysis of PK profiles and parameters. The patients will continue treatment until the occurrence of a DLT event, disease progression, intolerant toxicity, withdrawal of ICF, treatment discontinuation determined by the investigator, lost to follow-up, death, or termination of the study, (whichever occurs first).

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
12
Inclusion Criteria
  • Histologically confirmed diagnosis o f non Hodgkin's lymphoma
  • Patients with non-Hodgkin's lymphoma who have either failed standard of care or are intolerant/unapplicable to therapy;
  • Subject who has no growth factor supportive therapy, transfusion of blood or blood products within 14 days before the enrollment test
  • The patient is capable and willing to accept the follow up according to the protocol and signed or provided the ICF signed by the legal representative
  • Contraceptive measures , definition of women of childbearing age and contraceptive requirements
Exclusion Criteria
  • Subjects who have received anti tumor therapy and have not recovered from previous toxicity reactions ( toxicity reactions unrecovered to grade 1 as per NCI CTCAE 5.0
  • Subjects who received major surgery (excluding diagnostic biopsy)within 28 days prior to the first dose.
  • Subjects who received autologous stem cell transplantation within 3 months or allogeneic stem cell transplantation within 6 months prior to the first dose with active graft versus host response at screening
  • Subjects with use of prohibited medication within 7 days or less than 5 half lives prior to the first dose (whichever is shorter), see prohibited medication list
  • Participated in other interventional clinical trial within 1 month or 5 half life periods prior to the first dose (whichever is longer), except for non intervention clinical trials
  • Evidence suggests that there may be human immunodeficiency virus (HIV) infection , or hepatitis C (HCV) hepatitis virus infection PCR RNA positive);
  • Uncontrolled systemic infection or infection requiring intravenous injection of antibiotics
  • Lymphoma with central nervous system (CNS) involvement
  • Subjects with concurrent other malignant tumors in addition to the studied tumor within 2 years prior to the first dosing , except for the controlled skin basal cell carcinoma , cervical carcinoma in situ, ductal carcinoma in situ , and papillary thyroid carcinoma
  • Subject is known to be allergic to the components of abexinostat
  • Pregnant and lactating subjects
  • Upon the investigator's judgment , the subject has any disease or medical condition that is unstable or may affect safety or study compliance , such as uncontrolled hypertension,uncontrolled diabetes, active bleeding , etc.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dosing CohortsAbexinostatThree (3) dose cohorts are pre-set to include 40 mg BID, 60 mg BID and 80 mg BID,respectively.The pre-set dose group is subject to change during the study and the actual dosage increment is determined by the Data safety Monitoring Committee (DSMC).
Primary Outcome Measures
NameTimeMethod
Determine the maximum tolerated doseUp to 6 month

Determine the maximum tolerated dose based on observed dose-limiting toxicity at different dose levels

Measure Cmax at Different Dose LevelUp to 6 month

Measure Peak Plasma Concentration (Cmax at different dose level

Measure AUC at Different Dose LevelUp to 6 month

Measure Area under the plasma concentration versus time curve (AUC) levels at different dose level

Secondary Outcome Measures
NameTimeMethod
Measure Objective Response RateUp to 12 Month

Measure objective response rate in % at the RP2D in patients with non-Hodgkin's lymphoma who have failed standard of care

Measure Duration of ResponseUp to 12 Month

Measure duration of response in months at the RP2D in patients with non-Hodgkin's lymphoma who have failed standard of care

Trial Locations

Locations (4)

Cancer Hospital Chinese Academy of Medical Sciences

🇨🇳

Beijing, China

Tianjin Medical University General Hospital

🇨🇳

Tianjin, China

The Affiliated Hospital of Xuzhou Medical University

🇨🇳

Xuzhou, China

Zhejiang Cancer Hospital

🇨🇳

Hangzhou, China

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