Peripheral T-cell Lymphoma
Conditions
Keywords
Belinostat, Peripheral T-cell lymphoma, PXD101, PTCL, HDAC inhibitor, Histone deacetylase inhibitor
Brief summary
The purpose of this study is to assess efficacy and safety of belinostat in participants with relapsed or refractory peripheral T-cell lymphoma (PTCL), who failed at least one prior systemic therapy.
Detailed description
This is an open-label, multicenter, single arm efficacy and safety study in participants with relapsed or refractory peripheral T-cell lymphoma, who have failed at least one prior systemic therapy. Approximately 120 participants will be enrolled. Participants will be treated with 1000 mg/m\^2 belinostat administered as a 30-minute IV infusion on Days 1-5 of every 3-week cycle until there is disease progression or unmanageable treatment-related toxicities. The primary study endpoint is objective response rate (ORR) based on the International Harmonization Project (IHP) revision International Working Group (IWG) criteria. Safety will be evaluated during the study and for 30 days after the last administration of study drug. Adverse events and laboratory studies will be graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v. 3.0.
Interventions
DRUGBelinostat
Sponsors
Valerio Therapeutics
Spectrum Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A histologically confirmed diagnosis of PTCL * Participants must have relapsed or refractory disease after at least one prior systemic anticancer regimen. Systemic anticancer therapy is defined as chemotherapy or immunotherapy administered systemically. * Participants must have at least one site of disease measurable in two dimensions by computed tomography (CT). * Age ≥ 18 years. * Adequate bone marrow, liver, and renal functions. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Negative pregnancy test for women of childbearing potential.
Exclusion criteria
* Relapse within 100 days of autologous or allogeneic bone marrow transplant. * Prior histone deacetylase (HDAC) inhibitor therapy. * Co-existing active infection or any medical condition likely to interfere with trial procedures. * Severe cardiovascular disease. * Clinically significant central nervous system disorders with altered mental status or psychiatric disorders precluding understanding of the informed consent process and/or completion of the necessary studies. * Active concurrent malignancy (except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix). * Symptomatic or untreated central nervous system (CNS) metastases. * Pregnant or breast-feeding women. * Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | 24 months | Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) according to International Working Group (IWG) criteria. The response was assessed based on clinical and radiological criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites. As pre-defined, the primary endpoint analysis for this study was based on the Independent Review Committee (IRC) assessment of response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | 24 months | Time to response was defined as the time (in weeks) from first administration of treatment until first response. Response is defined as complete response (CR) or partial response (PR). CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites. |
| Duration of Response | 24 months | The Duration of Response was assessed by IWG criteria per the IRC from the date the measurement criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that relapse or progression was documented. It was estimated by the Kaplan-Meier method. Response is defined as complete response (CR) or partial response (PR). CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites. |
| Time to Progression | 24 months | Time to progression was defined as the time (in months) from first administration of treatment to the date of disease progression based on tumor assessments made according to the IWG criteria as assessed by the IRC. The progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. |
| Overall Survival | 24 months | Overall Survival was the time from first administration of study treatment until the date of death. |
| Number of Participants With At Least One Serious Treatment-Emergent Adverse Event (TEAE) | 24 months | A TEAE was defined as an event with an onset date and time on or after the first dosing start date and time, or on or after the first dosing start date if the onset time was missing. A serious TEAE was any untoward medical occurrence that at any dose results in death, prolonged hospitalization, persistent or significant disability or congenital abnormalities. |
| Progression Free Survival | 24 months | Progression-free survival (PFS) was the duration of time from first administration of study treatment to date of first documented progression or death from any cause. It was based on tumor assessments made according to the IWG criteria as assessed by the IRC. The progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir. |
Other
| Measure | Time frame |
|---|---|
| Population Pharmacokinetics | 24 months |
Countries
Belgium, Canada, Croatia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Russia, Slovakia, South Africa, Spain, United Kingdom, United States
Participant flow
Pre-assignment details
Participants with relapsed or refractory T-Cell lymphoma who signed the informed consent form and met all Inclusion/Exclusion criteria were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Belinostat Belinostat 1000 mg/m\^2 administered as a 30 minute IV infusion on Days 1-5 of every 3-week cycle until disease progression or unmanageable treatment-related toxicities. | 129 |
| Total | 129 |
Baseline characteristics
| Characteristic | Belinostat |
|---|---|
| Age, Continuous | 63 years |
| Sex: Female, Male Female | 60 Participants |
| Sex: Female, Male Male | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 22 / 129 |
| other Total, other adverse events | 125 / 129 |
| serious Total, serious adverse events | 61 / 129 |
Outcome results
Primary
Objective Response Rate
Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) according to International Working Group (IWG) criteria. The response was assessed based on clinical and radiological criteria. CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites. As pre-defined, the primary endpoint analysis for this study was based on the Independent Review Committee (IRC) assessment of response.
Time frame: 24 months
Population: Efficacy Analysis Dataset included participants who received at least 1 dose of belinostat and had a confirmed peripheral T-cell lymphoma (PTCL) diagnosis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Belinostat | Objective Response Rate | 25.8 percentage of participants |
Secondary
Duration of Response
The Duration of Response was assessed by IWG criteria per the IRC from the date the measurement criteria were first met for CR or PR (whichever status was recorded first) until the first subsequent date that relapse or progression was documented. It was estimated by the Kaplan-Meier method. Response is defined as complete response (CR) or partial response (PR). CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites.
Time frame: 24 months
Population: Efficacy Analysis Dataset included participants who received at least 1 dose of belinostat and had a confirmed PTCL diagnosis. Overall number of participants analysed included responding participants (CR/PR) only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belinostat | Duration of Response | 13.6 months |
Secondary
Number of Participants With At Least One Serious Treatment-Emergent Adverse Event (TEAE)
A TEAE was defined as an event with an onset date and time on or after the first dosing start date and time, or on or after the first dosing start date if the onset time was missing. A serious TEAE was any untoward medical occurrence that at any dose results in death, prolonged hospitalization, persistent or significant disability or congenital abnormalities.
Time frame: 24 months
Population: Full Analysis Dataset included all participants who received at least 1 dose of belinostat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belinostat | Number of Participants With At Least One Serious Treatment-Emergent Adverse Event (TEAE) | 61 Participants |
Secondary
Overall Survival
Overall Survival was the time from first administration of study treatment until the date of death.
Time frame: 24 months
Population: Efficacy Analysis Dataset included participants who received at least 1 dose of belinostat and had a confirmed PTCL diagnosis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belinostat | Overall Survival | 7.9 months |
Secondary
Progression Free Survival
Progression-free survival (PFS) was the duration of time from first administration of study treatment to date of first documented progression or death from any cause. It was based on tumor assessments made according to the IWG criteria as assessed by the IRC. The progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time frame: 24 months
Population: Efficacy Analysis Dataset included participants who received at least 1 dose of belinostat and had a confirmed PTCL diagnosis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belinostat | Progression Free Survival | 1.6 months |
Secondary
Time to Progression
Time to progression was defined as the time (in months) from first administration of treatment to the date of disease progression based on tumor assessments made according to the IWG criteria as assessed by the IRC. The progression is defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.
Time frame: 24 months
Population: Efficacy Analysis Dataset included participants who received at least 1 dose of belinostat and had a confirmed PTCL diagnosis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belinostat | Time to Progression | 2 months |
Secondary
Time to Response
Time to response was defined as the time (in weeks) from first administration of treatment until first response. Response is defined as complete response (CR) or partial response (PR). CR is defined as the disappearance of all evidence of disease. PR is defined as a regression of measurable disease and no new sites.
Time frame: 24 months
Population: Efficacy Analysis Dataset included participants who received at least 1 dose of belinostat and had a confirmed PTCL diagnosis. Overall number of participants analyzed included responding participants (CR/PR) only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Belinostat | Time to Response | 5.6 weeks |
Other Pre-specified
Population Pharmacokinetics
Time frame: 24 months