A Phase 1 Open-label Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of HBI-8000 in Japanese Patients With Non Hodgkin's Lymphoma

HUYABIO International, LLC.8 sites in 1 country13 target enrollmentMarch 2014

ConditionsNon-Hodgkin's Lymphoma

InterventionsHBI-8000

DrugsHBI-8000

Overview

Phase: Phase 1
Intervention: HBI-8000
Conditions: Non-Hodgkin's Lymphoma
Sponsor: HUYABIO International, LLC.
Enrollment: 13
Locations: 8
Primary Endpoint: Maximum tolerated dose (MTD) of HBI-8000 in adult Japanese patients with non Hodgkin's lymphoma (NHL) for whom no other standard therapy is suitable based on the frequency of dose-limiting toxicities (DLTs) which occur within 28 days.
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Phase 1, open-label, non-randomized, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of HBI-8000 administered orally.

Detailed Description

Phase 1, open-label, non-randomized, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of HBI-8000 administered orally. Patients must be hospitalized as per guidance of the treating investigator throughout Cycle 1. Patients will receive HBI 8000 twice weekly (BIW) (after breakfast), in 28 day treatment cycles. Patients will be enrolled in cohorts of 3 patients. The first cohort of 3 patients will receive 30 mg BIW. Decisions regarding cohort escalation will be based upon the clinical experience in Cycle 1 (first 28 days) only. For a given cohort, if 1 patient enrolled in the cohort experiences a dose limiting toxicity (DLT) within 28 days of the first dose, the cohort will be expanded to 6 patients.

Registry

clinicaltrials.gov

Start Date

March 2014

End Date

October 2016

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

HUYABIO International, LLC.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically or cytologically diagnosed non Hodgkin's lymphoma patients for whom no other standard therapy is available
•Male or female, aged 20 years or over at time of signing informed consent
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and life expectancy, per the investigator, of more than 3 months at time of signing informed consent
•Patients for whom at least 1 measurable lesion is confirmed in the lesion assessment before the start of study drug administration
•Patients must have recovered to Grade 1 or less (Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.03) from all toxicity associated with previous chemotherapy, antibody, or radiotherapy. (Exception: patients may enter with continuing alopecia regardless of CTCAE grade.) The following intervals between ending of another treatment and starting of HBI-8000 must elapse:
•Chemotherapy: 4 weeks
•Nitrosourea: 6 weeks
•Radiotherapy: 4 weeks
•Major surgery: 4 weeks
•Immunomodulatory drugs: 4 weeks

Exclusion Criteria

•Patients with current, previous, or clinically suspected invasion of the central nervous system (CNS)
•Organ transplant recipients
•Allogeneic stem cell transplant recipients
•Previous extensive radiotherapy involving ≥30% of hematopoietic bone marrow, excluding patients who have had total body irradiation as part of a conditioning regimen for ASCT
•Patients with an electrocardiogram (ECG) finding at screening of QT interval corrected for heart rate using Fridericia's method (QTcF) prolongation \>450 ms in male patients and \>470 ms in female patients, ventricular tachycardia, ventricular fibrillation, second- or third-degree heart block, unstable angina, coronary angioplasty or stenting, myocardial infarction, chronic congestive heart failure (New York Heart Association Class III or IV) within 6 months of starting the study drug, any cardiomyopathy, or long QT syndrome
•Any condition including the presence of laboratory abnormalities, which, as judged by the investigator, places the patient at unacceptable risk if he/she were to participate in the study. Examples of such medical conditions are, but are not limited to, as follows:
•Uncontrolled diabetes mellitus (e.g., glycosylated hemoglobin \[HbA1c\] \>8%), as judged by the investigator
•Patients who have had any of the following abnormal measurements at screening performed within 2 weeks (14 days) prior to the start of study drug administration:
•Hemoglobin: \<8 g/dL
•Neutrophil count: \<1,200/µL

Arms & Interventions

HBI-8000

HBI-8000 at the assigned dose twice weekly.

Intervention: HBI-8000

Outcomes

Primary Outcomes

Maximum tolerated dose (MTD) of HBI-8000 in adult Japanese patients with non Hodgkin's lymphoma (NHL) for whom no other standard therapy is suitable based on the frequency of dose-limiting toxicities (DLTs) which occur within 28 days.

Time Frame: 28 days

Secondary Outcomes

Pharmacokinetic parameter: time of maximum observed plasma concentration (Tmax) at 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 12, 24, 48, and 72 hours.(28 days)
Pharmacokinetic parameter: area under the plasma concentration-time curve (AUC) measurement at 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 12, 24, 48, and 72 hours.(28 days)
Pharmacokinetic parameter: maximum observed plasma concentration (Cmax) measurement at 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 12, 24, 48, and 72 hours.(28 days)
Pharmacokinetic parameter: apparent terminal half-life (T1/2) at 0.5, 0.75, 1, 1.5, 2, 2.5, 4, 6, 12, 24, 48, and 72 hours.(28 days)
Safety of HBI-8000 in Japanese patients with NHL for whom no other standard therapy is suitable with incidence and severity of adverse events graded according to the NCI-CTCAE version 4.03(Through study completion, an average of 24 weeks.)
Anti-tumor activity of HBI-8000 by overall response status based on Cheson's response criteria for NHL and Japan Clinical Oncology Group (JCOG) response criteria for Adult T-Cell Lymphoma (ATL)(Through study completion, an average of 24 weeks.)