Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL)

NCT02955589 | Completed Phase 2 Results DMC

• 1 other identifier: HBI-8000-210
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 15

Brief 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)

Conditions

Adult T-Cell Lymphoma (ATL)

Outcome Measures

Primary Outcomes (1)

• 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.

  Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.

Secondary Outcomes (3)

• Objective Response Rate by Disease Subtype

  Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.

• Median Duration of Progression-free Survival (PFS)

  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)

  Through the end of the study (up to 12 months).

Other Outcomes (2)

• Median Duration of Overall Survival (OS)

  Until death, assessed every 3 months up to 12 months after last treatment through the end of the study (up to 30 months).

• Safety and Tolerability, Evaluated as Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

  From date of first subject's consent until 30 days after last treatment, assessed up to 25 months.

Study Arms (1)

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.

Drug: HBI-8000

Interventions

HBI-8000 DRUG

Oral, twice weekly

HBI-8000

Eligibility Criteria

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

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• HUYABIO International, LLC.: lead
• Iqvia Pty Ltd: collaborator

Study Sites (15)

Unknown Facility

Fukuoka, Japan

Location

Unknown Facility

Isehara, Japan

Location

Unknown Facility

Kagoshima, Japan

Location

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Miyagi, Japan

Location

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Miyazaki, Japan

Location

Unknown Facility

Nagasaki, Japan

Location

Unknown Facility

Nagoya, Japan

Location

Unknown Facility

Okinawa, Japan

Location

Unknown Facility

Ōita, Japan

Location

Unknown Facility

Ōmura, Japan

Location

Unknown Facility

Saitama, Japan

Location

Unknown Facility

Sapporo, Japan

Location

Unknown Facility

Suita, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Unknown Facility

Yufu, Japan

Location

Related Publications (1)

• 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.

  PMID: 35579212 RESULT

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

HBI-8000

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Huya Japan clinical development
• Organization: Huya Japan G.K.

japanclinical@huyabio.com

Study Officials

• Gloria Lee, MD

  HUYA Bioscience International, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 4, 2016
• Study Start: November 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: November 1, 2019
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (15)