Safety Study of HBI-8000 in Japanese Patients With Non Hodgkin's Lymphoma

NCT02697552 | Completed Phase 1 DMC

• 1 other identifier: HBI-8000-201
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 8

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.

Conditions

Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days

Secondary Outcomes (6)

• 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: 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: 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

• 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.

Study Arms (1)

HBI-8000

EXPERIMENTAL

HBI-8000 at the assigned dose twice weekly.

Drug: HBI-8000

Interventions

HBI-8000 DRUG

Oral doses of 30mg, 40mg, 50mg twice weekly \[BIW\].

Also known as: Chidamide, CS055

HBI-8000

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Any antibody agent: 12 weeks (84 days)
• Autologous stem cell transplantation (ASCT): 12 weeks (84 days)
• Patients must agree not to consume grapefruit, grapefruit juices, Seville oranges, St.John's wort, or any products containing Seville oranges, grapefruit, or St. John's wort during their participation on the study
• Patients who signed the informed consent form and are capable of giving informed consent in accordance with the policies of the Institutional Review Board (IRB)
• Patients must be willing to be hospitalized as per guidance of the treating investigator throughout Cycle 1

You may not qualify if:

• 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
• Platelet count: \<75,000/µL
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT): \>3 x the upper limit of normal (ULN)
• Bilirubin level: \>1.5 x ULN
• Creatinine clearance: \<50 mL/min via Cockcroft-Gault formula ; proteinuria \> Grade 2
• Plasma troponin I (or troponin T): \>ULN

Sponsors & Collaborators

• HUYABIO International, LLC.: lead

Study Sites (8)

Nagoya City University Hospital

Aichi, Japan

Location

Fukuoka University Hospital

Fukuoka, Japan

Location

NHO Kyushu Cancer Center

Fukuoka, Japan

Location

Kagoshima University Medical and Dental Hospital

Kagoshima, Japan

Location

Tokai University Hospital

Kanagawa, Japan

Location

NHO Kumamoto Medical Center

Kumamoto, Japan

Location

NHO Nagasaki Medical Center

Nagasaki, Japan

Location

National Cancer Center Hospital

Tokyo, Japan

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

HBI-8000; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Kensei Tobinai, MD

  National Cancer Center Hospital Tokyo, Japan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2016
• First Posted: March 3, 2016
• Study Start: March 1, 2014
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: January 12, 2017

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

JP (8)