Non-Hodgkin's LymphomaPhase 1NCT02697552
Safety Study of HBI-8000 in Japanese Patients With Non Hodgkin's Lymphoma
A Phase 1 study testing HBI-8000 in people with Non-Hodgkin's Lymphoma, run by HUYABIO International, LLC. at 8 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Non-Hodgkin's Lymphoma
- What is being tested?
- HBI-8000
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 8 sitesJapan
- Study dates
- Mar 2014to Oct 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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
- Prothrombin time or activated partial thromboplastin time: >1.25 x ULN
- Potassium, corrected calcium , or magnesium levels outside normal limits
- Any cardiac arrhythmia requiring anti-arrhythmic medication
- Patients with a history of seizures
- Patients with known hypersensitivity to histone deacetylase (HDAC) inhibitors or any of the components of the HBI-8000 tablets
- Patients with a history or complication of malignant tumors, unless the patients have been free of the disease for 5 years or longer, except the following, if successfully treated, in which case they are not excluded:
- Basal cell carcinoma of the skin
- Squamous cell carcinoma of the skin
- Cervical carcinoma in situ
- Carcinoma in situ of the breast
- An incidental histological finding of prostate carcinoma (TNM stage T1a or T1b)
- Early-stage gastric cancer treated with endoscopic mucosal resection or endoscopic submucosal dissection
- Patients with uncontrolled inter-current infection
- Patients with active clinically significant bleeding or recently occurred thrombotic diseases, including patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic prophylaxis
- Women who are pregnant, women who are not willing to stop breastfeeding during study period and for 10 days after the last dose of study drug, women of child bearing potential, or men with a sexual partner of child bearing potential who are not willing to use double-barrier method during study period and at least 3 months (for men) or at least 1 month (for women) after the last dose of study drug. Double-barrier method is defined as a combination of 2 effective contraceptive methods, such as condom or condom containing spermicide in combination with a diaphragm, oral contraceptive, or intrauterine device.
- Note: Female subjects will be considered to be a woman of childbearing potential unless having undergone permanent contraception or postmenopausal. Postmenopausal is defined as at least 12 months without menses with no other medical reasons (i.e., chemical menopause because of treatment with anti-malignant tumor agents).
- Seropositivity for the human immunodeficiency virus (HIV) antibody
- Hepatitis B surface antigen-positive, or hepatitis C virus antibody positive. In case hepatitis B core antibody and/or hepatitis B surface antibody is positive even if hepatitis B surface antigen negative, a hepatitis B virus deoxyribonucleic acid (DNA) test [real-time polymerase chain reaction (PCR]) measurement] should be performed and if positive, the patient should be excluded
- Patients who were in other experimental clinical studies with investigational agents within 30 days before the start of study drug administration (12 weeks for any investigational antibody therapy or investigational ASCT), or in current clinical studies with investigational agents
- Patients with a history of drug abuse or long-term excessive alcohol consumption which could affect study result assessment
- Patients considered by the investigator to be unsuitable for the study because of any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study, or because of any condition that confounds the ability to interpret data from the study
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
Japan8 sites
Nagoya City University Hospital
Aichi
Fukuoka University Hospital
Fukuoka
NHO Kyushu Cancer Center
Fukuoka
Kagoshima University Medical and Dental Hospital
Kagoshima
Tokai University Hospital
Kanagawa
NHO Kumamoto Medical Center
Kumamoto
NHO Nagasaki Medical Center
Nagasaki
National Cancer Center Hospital
Tokyo
About this study
Official title: 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
Phase 1, open-label, non-randomized, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of HBI-8000 administered orally.
Read the 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.
- Conditions
- Non-Hodgkin's Lymphoma
- Being tested
- HBI-8000
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HBI-8000Drug
Also called Chidamide, CS055
Oral doses of 30mg, 40mg, 50mg twice weekly [BIW].
| Study group | Role | What they receive |
|---|---|---|
| HBI-8000 | Experimental | HBI-8000 at the assigned dose twice weekly. Receives: Drug: HBI-8000 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Plasma concentration of HBI-8000 will be measured following single dose (Days 1-4) and multiple dose (Days 25-28) administration
Measured: 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.
Plasma concentration of HBI-8000 will be measured following single dose (Days 1-4) and multiple dose (Days 25-28) administration
Measured: 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.
Plasma concentration of HBI-8000 will be measured following single dose (Days 1-4) and multiple dose (Days 25-28) administration
Measured: 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.
Plasma concentration of HBI-8000 will be measured following single dose (Days 1-4) and multiple dose (Days 25-28) administration
Measured: 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)
Measured: Through study completion, an average of 24 weeks.
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
Measured: Through study completion, an average of 24 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2016 (estimated)
- Study startMar 2014
- Primary completionOct 2016
- Study completionOct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- HUYABIO International, LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kensei Tobinai, MD, Principal investigator, National Cancer Center Hospital Tokyo, Japan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02697552
- Sponsor's protocol ID
- HBI-8000-201
- Status last verified
- Oct 2016
- First submitted
- 17 Feb 2016
- Last updated
- 12 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02697552
- Acronym / sponsor ID
- HBI-8000-201
- Conditions
- Non-Hodgkin's Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- HUYABIO International, LLC.Industry (pharma, biotech, devices)
- Study start
- Mar 2014
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 3 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBI-8000 | Experimental | Drug: HBI-8000HBI-8000 at the assigned dose twice weekly. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
Key exclusion criteria (36 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HBI-8000Also: Chidamide, CS055Oral doses of 30mg, 40mg, 50mg twice weekly [BIW]. | Drug | HBI-8000 |
Primary outcome
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
6 secondary outcomes
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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)
Time frame: Through study completion, an average of 24 weeks.
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
Time frame: Through study completion, an average of 24 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kensei Tobinai, MD principal investigator
National Cancer Center Hospital Tokyo, Japan
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HBI-8000 in people with Non-Hodgkin's Lymphoma, run by HUYABIO International, LLC. at 8 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2017.