Adult T-Cell Lymphoma (ATL)Phase 2NCT02955589
Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL)
A Phase 2 study testing HBI-8000 in people with Adult T-Cell Lymphoma (ATL), run by HUYABIO International, LLC. at 15 sites in Japan.
Trial summary
Phase 2b, open-label, non-randomized, single arm study to evaluate the safety, and efficacy of HBI-8000 40 mg BIW in patients with relapsed or refractory ATL (R/R ATL) Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Adult T-Cell Lymphoma (ATL)
- 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
- 23 participants
- Where
- 15 sitesJapan
- Study dates
- Nov 2016to Nov 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histopathological, or cytological diagnosis of ATL confirmed as seropositive for anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody
- Acute, lymphoma or unfavorable chronic types. The unfavorable chronic type is defined by the presence of at least 1 of the following: serum albumin <3.5 g/dL, lactic dehydrogenase (LDH) >300 U/L, or blood urea nitrogen (BUN) >25 mg/dL. The patient must have at least 1 of measurable lesion, or evaluable lesion in either of peripheral blood or skin
- Relapsed or refractory disease after receiving prior systemic therapy with mogamulizumab, or ≥1 prior systemic therapy with cytotoxic chemotherapy in case of intolerance/contraindication for mogamulizumab. And there is no other standard treatment which can be considered appropriate for patients
- Male or female, aged 20 years or older
- ECOG Performance Status of 0-2
- Life expectancy of greater than 3 months
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- Meeting the following baseline laboratory criteria for screening:
- Absolute Neutrophil Count >1500/µL independent of growth factor support within 7 days
- Platelets >75,000/µL independent of transfusion within 14 days
- Hgb >8 g/dL independent of transfusion within 14 days
- Serum creatinine < 1.5 X upper limit of normal (ULN)
- Serum aspartate aminotransferase/glutamyl oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/glutamyl pyruvic transaminase (ALT/SGPT) less than or equal to 3 X ULN
- Serum Bilirubin less than or equal to 1.5 X ULN
- Negative serum pregnancy test for females of childbearing (reproductive) potential. Female patients of child bearing potential must use an effective method of birth control (e.g., hormonal contraceptive, intrauterine device, diaphragm with spermicide or condom with spermicide) during treatment period and 1 month thereafter; Males must use an effective method of birth control (2 barrier methods) during treatment period and 3 months thereafter.
- Note: Female patients will be considered to be women 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 (e.g., chemical menopause because of treatment with anti-malignant tumor agents).
- Signed informed consent
Who cannot join
- 2.5.2 Exclusion Criteria:
- Patients in whom central nervous system lymphoma is recognized during screening (if suspected clinically, imaging study should be performed to confirm)
- Male patients with QTcF > 450 msec at screening, female patients with QTcF > 470 msec at screening, or patients with congenital long QT syndrome, clinically significant arrhythmia, history of congestive heart failure (New York Heart Association Class III or IV) or acute myocardial infarction within 6 months of starting the study drug at screening.
- Patients with known hypersensitivity to benzamide class of compounds or any of the components of HBI-8000 tablets, and patients with prior exposure of HBI-8000;
- Patients with a history of second malignancy other than disease under study. The exceptions are disease (excluding disease listed below) that has been treated with curative intent with no evidence of recurrence in past 5 years. Furthermore, if the second malignancy is one of the following diseases that were treated with curative intent, it is only required that there is no evidence of recurrence in past 2 years;
- Basal cell carcinoma of the skin
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- 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
- Autologous stem cell transplantation within 12 weeks (84 days) of starting the study drug
- History of allogeneic stem cell transplantation
- Organ transplantation recipients except autologous hematopoietic stem cell transplantation
- Uncontrolled inter-current infection
- 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 DNA test (real-time PCR measurement) should be performed and if positive, the patient should be excluded from study
- Any history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
- Uncontrolled diabetes mellitus, hypertension, endocrine disorder, bleeding disorder
- Major surgery or radiation therapy within 28 days of starting the study drug
- Receiving investigational agents or anti-cancer therapy within 28 days, nitrosourea or mitomycin C within 42 days, of starting the study drug
- Receiving antibody therapy for ATL within 4 weeks of starting the study drug
- Women who are breastfeeding or women who are not willing to stop breastfeeding during study treatment period and for 30 days after the last dose of study drug
- Potential for non-compliance or at increased risk based on investigator's judgement
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Japan15 sites
Study site
Fukuoka
Study site
Isehara
Study site
Kagoshima
Study site
Miyagi
Study site
Miyazaki
Study site
Nagasaki
Study site
Nagoya
Study site
Ōita
Study site
Okinawa
Study site
Ōmura
Study site
Saitama
Study site
Sapporo
Study site
Suita
Study site
Tokyo
Study site
Yufu
About this study
Official title: A Phase 2b Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL)
Phase 2b, open-label, non-randomized, single arm study to evaluate the safety, and efficacy of HBI-8000 40 mg BIW in patients with relapsed or refractory ATL (R/R ATL)
Read the detailed description
This is a Phase 2b, open-label, non-randomized, single arm study to evaluate the safety, and efficacy of HBI-8000 40 mg BIW in patients with relapsed or refractory ATL (R/R ATL). HBI 8000 will be administered orally approximately 30 minutes after any regular meal twice a week. There will be 3 to 4 days between dosing. A treatment cycle is defined as 28 consecutive days. HBI-8000 administration will be continued until disease progression or unacceptable toxicities are observed despite appropriate dose reduction or treatment interruption.
- Conditions
- Adult T-Cell Lymphoma (ATL)
- Being tested
- HBI-8000
- Medical subject headings
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HBI-8000Drug
Oral, twice weekly
| Study group | Role | What they receive |
|---|---|---|
| HBI-8000 | Experimental | Four 10 mg tablets or less twice weekly orally approximately 30 minutes after any regular meal. The treatment will be continuous, with 3-4 days between dosing. Treatment will continue until disease progression in the absence of unacceptable toxicity. Receives: Drug: HBI-8000 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Objective response rate (CR+CRu+PR) was determined based on the response of all compartments (lymph nodes, extranodal masses, spleen \& liver, skin, peripheral blood, and bone marrow) per Tsukasaki criteria and skin lesions were evaluated according to modified SWAT.
CR: The disappearance of all disease whereby all criteria met; All compartments are normal.
CRu: Lymph nodes ≥75% decrease and extranodal masses ≥75% decrease, but presence of residual lesion; spleen, liver, skin, peripheral blood and bone marrow are normal.
PR: Lymph nodes and extradnodal masses - Reduction rate of the sum of 2 dimension products of ≥50% and ≤75%, no increase spleen /liver, skin lesion ≥50% decrease and peripheral blood ≥50% decrease.
Measured: Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.
Secondary outcomes (3)
Objective Response Rate by Disease Subtype
Objective response rate (CR+CRu+PR) by disease subtype (acute ATL, lymphoma ATL, unfavorable chronic ATL) was determined based on the response of all compartments (lymph nodes, extranodal masses, spleen \& liver, skin, peripheral blood, and bone marrow) per Tsukasaki criteria and skin lesions were evaluated according to modified SWAT.
Measured: Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.
Median Duration of Progression-free Survival (PFS)
PFS was defined as the duration from the date of the first study drug dose to the disease progression or death, whichever occurs first. Evaluation of progression/progressive disease is performed according to the modified criteria of the International Consensus Meeting. Progression is defined as a 50% increase in the sum of 2-dimension products of nodal and/or extra nodal lesions, or 25% increase of mSWAT score in skin lesion, or 50% increase of absolute count of abnormal lymphocyte, or the appearance of new lesions.
Measured: From the first day of HBI-8000 dose to the day of disease progression or death, which ever came first, through the end of the study (up to 15 months).
Median Duration of Response (DOR)
Median duration of response from first response CR, CRu, PR, date to progression, death or last available tumor assessment.
Measured: Through the end of the study (up to 12 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2016 (estimated)
- Study startNov 2016
- Primary completionDec 2018
- Study completionNov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adult T-Cell Lymphoma (ATL)Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- HUYABIO International, LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Responsible party
- Sponsor
- Investigators
- Gloria Lee, MD, Study chair, HUYA Bioscience International, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02955589
- Sponsor's protocol ID
- HBI-8000-210
- Status last verified
- May 2024
- First submitted
- 1 Nov 2016
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Utsunomiya A, Izutsu K, Jo T, Yoshida S, Tsukasaki K, Ando K, Choi I, Imaizumi Y, Kato K, Kurosawa M, Kusumoto S, Miyagi T, Ohtsuka E, Sasaki O, Shibayama H, Shimoda K, Takamatsu Y, Takano K, Yonekura K, Makita S, Taguchi J, Gillings M, Onogi H, Tobinai K. Oral histone deacetylase inhibitor tucidinostat (HBI-8000) in patients with relapsed or refractory adult T-cell leukemia/lymphoma: Phase IIb results. Cancer Sci. 2022 Aug;113(8):2778-2787. doi: 10.1111/cas.15431. Epub 2022 Jun 7.
PubMed 35579212
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b Open-Label Single-Arm Study to Evaluate the Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL)
- ClinicalTrials.gov ID
- NCT02955589
- Acronym / sponsor ID
- HBI-8000-210
- Conditions
- Adult T-Cell Lymphoma (ATL)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- HUYABIO International, LLC.Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Study start
- Nov 2016
- Primary completion
- Dec 2018 (actual)
- Study completion
- Nov 2019 (actual)
- First posted
- 4 Nov 2016 (estimated)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 2b, open-label, non-randomized, single arm study to evaluate the safety, and efficacy of HBI-8000 40 mg BIW in patients with relapsed or refractory ATL (R/R ATL)
Detailed description
This is a Phase 2b, open-label, non-randomized, single arm study to evaluate the safety, and efficacy of HBI-8000 40 mg BIW in patients with relapsed or refractory ATL (R/R ATL). HBI 8000 will be administered orally approximately 30 minutes after any regular meal twice a week. There will be 3 to 4 days between dosing. A treatment cycle is defined as 28 consecutive days. HBI-8000 administration will be continued until disease progression or unacceptable toxicities are observed despite appropriate dose reduction or treatment interruption.
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-8000Four 10 mg tablets or less twice weekly orally approximately 30 minutes after any regular meal. The treatment will be continuous, with 3-4 days between dosing. Treatment will continue until disease progression in the absence of unacceptable toxicity. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histopathological, or cytological diagnosis of ATL confirmed as seropositive for anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody
- Acute, lymphoma or unfavorable chronic types. The unfavorable chronic type is defined by the presence of at least 1 of the following: serum albumin <3.5 g/dL, lactic dehydrogenase (LDH) >300 U/L, or blood urea nitrogen (BUN) >25 mg/dL. The patient must have at least 1 of measurable lesion, or evaluable lesion in either of peripheral blood or skin
- Relapsed or refractory disease after receiving prior systemic therapy with mogamulizumab, or ≥1 prior systemic therapy with cytotoxic chemotherapy in case of intolerance/contraindication for mogamulizumab. And there is no other standard treatment which can be considered appropriate for patients
- Male or female, aged 20 years or older
- ECOG Performance Status of 0-2
Key exclusion criteria (23 listed)
- Patients in whom central nervous system lymphoma is recognized during screening (if suspected clinically, imaging study should be performed to confirm)
- Male patients with QTcF > 450 msec at screening, female patients with QTcF > 470 msec at screening, or patients with congenital long QT syndrome, clinically significant arrhythmia, history of congestive heart failure (New York Heart Association Class III or IV) or acute myocardial infarction within 6 months of starting the study drug at screening.
- Patients with known hypersensitivity to benzamide class of compounds or any of the components of HBI-8000 tablets, and patients with prior exposure of HBI-8000;
- Patients with a history of second malignancy other than disease under study. The exceptions are disease (excluding disease listed below) that has been treated with curative intent with no evidence of recurrence in past 5 years. Furthermore, if the second malignancy is one of the following diseases that were treated with curative intent, it is only required that there is no evidence of recurrence in past 2 years;
- Autologous stem cell transplantation within 12 weeks (84 days) of starting the study drug
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-8000Oral, twice weekly | Drug | HBI-8000 |
Primary outcome
Objective Response Rate
Time frame: Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.
Objective response rate (CR+CRu+PR) was determined based on the response of all compartments (lymph nodes, extranodal masses, spleen \& liver, skin, peripheral blood, and bone marrow) per Tsukasaki criteria and skin lesions were evaluated according to modified SWAT. CR: The disappearance of all disease whereby all criteria met; All compartments are normal. CRu: Lymph nodes ≥75% decrease and extranodal masses ≥75% decrease, but presence of residual lesion; spleen, liver, skin, peripheral blood and bone marrow are normal. PR: Lymph nodes and extradnodal masses - Reduction rate of the sum of 2 dimension products of ≥50% and ≤75%, no increase spleen /liver, skin lesion ≥50% decrease and peripheral blood ≥50% decrease.
3 secondary outcomes
Objective Response Rate by Disease Subtype
Time frame: Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.
Median Duration of Progression-free Survival (PFS)
Time frame: From the first day of HBI-8000 dose to the day of disease progression or death, which ever came first, through the end of the study (up to 15 months).
Median Duration of Response (DOR)
Time frame: Through the end of the study (up to 12 months).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 35579212Utsunomiya A, Izutsu K, Jo T, Yoshida S, Tsukasaki K, Ando K, Choi I, Imaizumi Y, Kato K, Kurosawa M, Kusumoto S, Miyagi T, Ohtsuka E, Sasaki O, Shibayama H, Shimoda K, Takamatsu Y, Takano K, Yonekura K, Makita S, Taguchi J, Gillings M, Onogi H, Tobinai K. Oral histone deacetylase inhibitor tucidinostat (HBI-8000) in patients with relapsed or refractory adult T-cell leukemia/lymphoma: Phase IIb results. Cancer Sci. 2022 Aug;113(8):2778-2787. doi: 10.1111/cas.15431. Epub 2022 Jun 7.
- 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.
Gloria Lee, MD study chair
HUYA Bioscience International, LLC
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HBI-8000 in people with Adult T-Cell Lymphoma (ATL), run by HUYABIO International, LLC. at 15 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 16 inclusion and 23 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 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response Rate (time frame: Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02955589, which also lists 1 linked publication.
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 19 Sep 2024.