Adult T-Cell Lymphoma (ATL)
Conditions
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)
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.
Interventions
DRUGHBI-8000
Oral, twice weekly
Sponsors
Iqvia Pty Ltd
HUYABIO International, LLC.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histopathological, or cytological diagnosis of ATL confirmed as seropositive for anti-Human T-lymphotrophic Virus type-I (HTLV-I) antibody 2. 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 3. 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 4. Male or female, aged 20 years or older 5. ECOG Performance Status of 0-2 6. Life expectancy of greater than 3 months 7. 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 8. 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). 9. Signed informed consent
Exclusion criteria
2.5.2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate by Disease Subtype | Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months. | 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. |
| 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). | 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. |
| Median Duration of Response (DOR) | Through the end of the study (up to 12 months). | Median duration of response from first response CR, CRu, PR, date to progression, death or last available tumor assessment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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). | Median duration of overall survival is from start of the study to death. |
| 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. | Safety and tolerability, evaluated as number of participants with treatment-related adverse events as assessed by CTCAE v4.0. |
Countries
Japan
Participant flow
Recruitment details
One more patient than planned consented.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | HBI-8000 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 22 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 73.4 Years STANDARD_DEVIATION 7.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 23 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment Japan | 23 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 15 Participants |
| Sub-Type of ATL at Screening Acute ATL | 13 Participants |
| Sub-Type of ATL at Screening Lymphoma ATL | 8 Participants |
| Sub-Type of ATL at Screening Unfavorable Chronic ATL | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 23 |
| other Total, other adverse events | 23 / 23 |
| serious Total, serious adverse events | 7 / 23 |
Outcome results
Primary
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.
Time frame: Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.
Population: Per Protocol Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBI-8000 | Objective Response Rate | 7 Participants |
Secondary
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.
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).
Population: Per Protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HBI-8000 | Median Duration of Progression-free Survival (PFS) | 7.6 Weeks |
Secondary
Median Duration of Response (DOR)
Median duration of response from first response CR, CRu, PR, date to progression, death or last available tumor assessment.
Time frame: Through the end of the study (up to 12 months).
Population: Per Protocol Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HBI-8000 | Median Duration of Response (DOR) | 40.0 Weeks |
Secondary
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.
Time frame: Tumor response was assessed until disease progression or unacceptable toxicity, up to 15 months.
Population: Per Protocol Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBI-8000 | Objective Response Rate by Disease Subtype | 6 Participants |
| HBI-8000 Lymphoma ATL | Objective Response Rate by Disease Subtype | 1 Participants |
| HBI-8000 Unfavorable Chronic ATL | Objective Response Rate by Disease Subtype | 0 Participants |
Other Pre-specified
Median Duration of Overall Survival (OS)
Median duration of overall survival is from start of the study to death.
Time frame: 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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HBI-8000 | Median Duration of Overall Survival (OS) | 34.4 Weeks |
Other Pre-specified
Safety and Tolerability, Evaluated as Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Safety and tolerability, evaluated as number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
Time frame: From date of first subject's consent until 30 days after last treatment, assessed up to 25 months.
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBI-8000 | Safety and Tolerability, Evaluated as Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | 23 Participants |