Trial Outcomes & Findings for Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL) (NCT NCT02955589)

Last Updated: 2024-09-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

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

Results posted on

2024-09-19

Participant Flow

One more patient than planned consented.

Participant milestones

Participant milestones
Measure	HBI-8000 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. HBI-8000: Oral, twice weekly
Overall Study STARTED	23
Overall Study COMPLETED	23
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HBI-8000 n=23 Participants 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. HBI-8000: Oral, twice weekly
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	22 Participants n=5 Participants
Age, Continuous	73.4 Years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	23 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Japan	23 participants n=5 Participants
Sub-Type of ATL at Screening Acute ATL	13 Participants n=5 Participants
Sub-Type of ATL at Screening Lymphoma ATL	8 Participants n=5 Participants
Sub-Type of ATL at Screening Unfavorable Chronic ATL	2 Participants n=5 Participants

PRIMARY outcome

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

Population: Per Protocol Set

Outcome measures

Outcome measures
Measure	HBI-8000 n=23 Participants 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. HBI-8000: Oral, twice weekly	HBI-8000 Lymphoma ATL 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. HBI-8000: Oral, twice weekly	HBI-8000 Unfavorable Chronic ATL 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. HBI-8000: Oral, twice weekly
Objective Response Rate	7 Participants	—	—

SECONDARY outcome

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

Population: Per Protocol Set

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.

Outcome measures

Outcome measures
Measure	HBI-8000 n=13 Participants 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. HBI-8000: Oral, twice weekly	HBI-8000 Lymphoma ATL n=8 Participants 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. HBI-8000: Oral, twice weekly	HBI-8000 Unfavorable Chronic ATL n=2 Participants 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. HBI-8000: Oral, twice weekly
Objective Response Rate by Disease Subtype	6 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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).

Population: Per Protocol Set

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.

Outcome measures

Outcome measures
Measure	HBI-8000 n=23 Participants 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. HBI-8000: Oral, twice weekly	HBI-8000 Lymphoma ATL 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. HBI-8000: Oral, twice weekly	HBI-8000 Unfavorable Chronic ATL 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. HBI-8000: Oral, twice weekly
Median Duration of Progression-free Survival (PFS)	7.6 Weeks Interval 3.4 to 32.1	—	—

SECONDARY outcome

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

Population: Per Protocol Set

Median duration of response from first response CR, CRu, PR, date to progression, death or last available tumor assessment.

Outcome measures

Outcome measures
Measure	HBI-8000 n=23 Participants 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. HBI-8000: Oral, twice weekly	HBI-8000 Lymphoma ATL 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. HBI-8000: Oral, twice weekly	HBI-8000 Unfavorable Chronic ATL 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. HBI-8000: Oral, twice weekly
Median Duration of Response (DOR)	40.0 Weeks Interval 11.4 to Upper limit was not reached due to insufficient number of participants with events	—	—

OTHER_PRE_SPECIFIED outcome

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

Population: Per Protocol Set

Median duration of overall survival is from start of the study to death.

Outcome measures

Outcome measures
Measure	HBI-8000 n=23 Participants 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. HBI-8000: Oral, twice weekly	HBI-8000 Lymphoma ATL 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. HBI-8000: Oral, twice weekly	HBI-8000 Unfavorable Chronic ATL 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. HBI-8000: Oral, twice weekly
Median Duration of Overall Survival (OS)	34.4 Weeks Interval 10.1 to 78.3	—	—

OTHER_PRE_SPECIFIED outcome

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

Population: Safety Analysis Set

Safety and tolerability, evaluated as number of participants with treatment-related adverse events as assessed by CTCAE v4.0.

Outcome measures

Outcome measures
Measure	HBI-8000 n=23 Participants 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. HBI-8000: Oral, twice weekly	HBI-8000 Lymphoma ATL 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. HBI-8000: Oral, twice weekly	HBI-8000 Unfavorable Chronic ATL 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. HBI-8000: Oral, twice weekly
Safety and Tolerability, Evaluated as Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	23 Participants	—	—

Adverse Events

HBI-8000

Serious events: 7 serious events

Other events: 23 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	HBI-8000 n=23 participants at risk 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. HBI-8000: Oral, twice weekly
Infections and infestations Urinary Tract Infection	4.3% 1/23 • Number of events 1 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Infections and infestations Pneumocystis jirovecii pneumonia	4.3% 1/23 • Number of events 1 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Cardiac disorders Palpitations	4.3% 1/23 • Number of events 1 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Platelet count decreased	8.7% 2/23 • Number of events 2 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	4.3% 1/23 • Number of events 1 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	4.3% 1/23 • Number of events 1 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Neutrophil count decreased	4.3% 1/23 • Number of events 1 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.

Other adverse events

Other adverse events
Measure	HBI-8000 n=23 participants at risk 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. HBI-8000: Oral, twice weekly
Blood and lymphatic system disorders Anaemia	34.8% 8/23 • Number of events 19 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Blood and lymphatic system disorders Thrombocytopenia	13.0% 3/23 • Number of events 29 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Gastrointestinal disorders Diarrhoea	26.1% 6/23 • Number of events 7 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Gastrointestinal disorders Abdominal pain	13.0% 3/23 • Number of events 3 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Gastrointestinal disorders Nausea	13.0% 3/23 • Number of events 4 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
General disorders Malaise	30.4% 7/23 • Number of events 10 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
General disorders Pyrexia	13.0% 3/23 • Number of events 5 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
General disorders Fatigue	13.0% 3/23 • Number of events 6 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Platelet count decreased	65.2% 15/23 • Number of events 64 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Neutrophil count decreased	47.8% 11/23 • Number of events 53 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations White blood cell count decreased	39.1% 9/23 • Number of events 47 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Weight decreased	17.4% 4/23 • Number of events 6 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Aspartate aminotransferase increased	8.7% 2/23 • Number of events 3 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Gamma-glutamyltransferase increased	8.7% 2/23 • Number of events 5 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Investigations Lymphocyte count decreased	8.7% 2/23 • Number of events 11 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Metabolism and nutrition disorders Decreased appetite	34.8% 8/23 • Number of events 11 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Metabolism and nutrition disorders Hypoalbuminaemia	13.0% 3/23 • Number of events 4 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Metabolism and nutrition disorders Hyponatraemia	8.7% 2/23 • Number of events 3 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Musculoskeletal and connective tissue disorders Back pain	17.4% 4/23 • Number of events 4 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Nervous system disorders Dysgeusia	17.4% 4/23 • Number of events 4 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.
Nervous system disorders Headache	8.7% 2/23 • Number of events 2 • From date of the first subject's consent to 12 months after last treatment, assessed up to 36 months.

Additional Information

Huya Japan clinical development

Huya Japan G.K.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Huya has agreements with PIs and the agreements restricts the right of the PI to discuss or publish trial results after the trial is completed. The content of disclosure restriction stated in the agreement is "PI shall obtain sponsor's prior written consent before disclosing the information obtained from this clinical trial to a professional society or other external party."
Publication restrictions are in place

Restriction type: OTHER