Peripheral T-Cell Lymphoma
Conditions
Keywords
Neoplasms, Neoplasms by Histologic Type, Lymphoma, Non-Hodgkin, T- Cell, Lymphatic Diseases, Lymphoproliferative Disorders, lmmune System Diseases, lmmunoproliferative Disorders
Brief summary
The purpose of this Phase 1 study is to determine the maximum tolerated dose (MTD) through observation of dose limiting toxicity (DLT), which is in advance defined, in patients with peripheral or cutaneous T-cell lymphoma.
Interventions
BIOLOGICALdenileukin diftitox (E7777)
E7777 will be administered by intravenous (IV) infusion for 5 days from Day 1 through 5 of each cycle (21 days/cycle) with 8 cycles in maximum for E7777 alone therapy. E7777 dose will be escalated from 6 micro-g/kg/day to 12, 15 and then to 18 in a stepwise fashion.
Sponsors
Eisai Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
lnclusion Criteria: * Male and female patients 20 to less than 80 years of age at the time of informed consent * Patients histologically or cytologically diagnosed to have peripheral T -cell lymphoma * Patients with a history of chemotherapy (including PUVA and retinoid) that resulted in relapse, recurrence and treatment resistance (just for the administration of E7777 alone) * Patients subject to CHOP therapy and without a history of prior treatment with anthracycline or anthraquinone anticancer drugs (just for the administration of E7777 in combination with CHOP therapy) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 * No carry-over of beneficial or adverse effects of the prior treatment that may affect the safety evaluation of the investigational drug (excluding Grade 1 neuropathy and alopecia)
Exclusion criteria
* Brain metastasis with clinical symptoms which requires treatment * Serious systemic infection requiring intensive treatment * Serious complications or histories * History of hypersensitivity to protein therapeutics * Known to be positive for HIV antibody, HCV antibody, or HBs antigen * History of malignancy other than peripheral T-cell lymphoma and less than five years have elapsed since the last remission * Patients who have undergone allogeneic hematopoietic stem cell transplantation * Patients with a relapse within 6 months after autologous hematopoietic stem-cell transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) and Recommended Dose (RD) | For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks) | The MTD was defined as the maximum tolerated dose observed after the evaluation of dose limiting toxicity (DLT) in Cycle 1 with 6 participants. If it was judged that the dose was not tolerated and DLT was confirmed in only 3 participants in the lower dose cohort, 3 other participants were to be added and tolerability was evaluated with 6 participants in total. The RD was to be comprehensively determined based on the MTD and safety data. Participants not evaluable for DLT were defined as participants found to be ineligible or in whom DLT evaluation was impossible due to premature termination for reasons other than toxicities in the judgement of the Sponsor, among those who had received at least one dose of the investigational drug after enrollment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of Denileukin Diftitox | Cycle 1 (Day 1) | Cmax was defined as the maximum observed concentration of denileukin diftitox following administration of study treatment on Cycle 1 Day 1 and was obtained directly from the measured serum concentration-time curves. Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a lower limit of quantitation (LLOQ) of 30 nanograms per milliliter (ng/mL). Serum pharmacokinetic (PK) data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Cmax, which was then summarized as the median and full range for all participants and expressed as ng/mL. |
| Time to Cmax (Tmax) of Denileukin Diftitox in Serum | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Tmax, which was then summarized as the median and full range for all participants and expressed in minutes. |
| Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t)) | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-t), which was then summarized as the median and full range for all participants and expressed as nanograms\*minutes per milliliter (ng\*min/mL). |
| Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-inf), which was then summarized as the median and full range for all participants and expressed as ng\*min/mL. |
| Terminal Phase Rate Constant (λz) | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of λz, which was then summarized as the median and full range for all participants and expressed in 1/minutes. |
| Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | From date of first dose up to 30 days after the last dose of study treatment, up to approximately 4 years 2 months | Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood coagulation, blood chemistry, and urinalysis values; periodic measurement of vital signs, body weight, 12-lead electrocardiograms (ECGs), Eastern Cooperative Oncology Group performance status, physical examination findings, and ophthalmological examination findings. TEAEs were defined as an AE that had an onset date, or worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to the last assessment. Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug. SAEs were defined as any untoward medical occurrence which results in death, was life-threatening, required hospitalization or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or caused a congenital anomaly/birth defect. |
| Volume of Distribution at Terminal Phase (Vz) | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vz, which was then summarized as the median and full range for all participants and expressed as milliliters per kilogram (mL/kg). |
| Volume of Distribution at Steady State (Vss) | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vss, which was then summarized as the median and full range for all participants and expressed as mL/kg. |
| Total Clearance (CL) | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. SerumPK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of CL, which was then summarized as the median and full range for all participants and expressed as milliliters/minutes/kilograms (mL/min/kg). |
| Recommended Dose | For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks) | This endpoint was combined with primary outcome measure, MTD |
| Terminal Elimination Phase Half-life (t1/2) | Cycle 1 (Day 1) | Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of t1/2, which was then summarized as the median and full range for all participants and expressed in minutes. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: 6 ug/kg/Day Denileukin Diftitox Denileukin diftitox was intravenously (IV) infused for 60 minutes (±10 minutes) daily from Day 1 through Day 5 of each Cycle (1 cycle = 3 weeks). | 3 |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox Denileukin diftitox was IV-infused for 60 minutes (±10 minutes) daily from Day 1 through Day 5 of each Cycle (1 cycle = 3 weeks). | 7 |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox Denileukin diftitox was IV-infused for 60 minutes (±10 minutes) daily from Day 1 through Day 5 of each Cycle (1 cycle = 3 weeks). | 3 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 1 |
| Overall Study | Disease Progression | 1 | 2 | 1 |
| Overall Study | Participant Choice | 1 | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: 6 ug/kg/Day Denileukin Diftitox | Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Total |
|---|---|---|---|---|
| Age, Continuous | 69.7 Years STANDARD_DEVIATION 5.51 | 49.9 Years STANDARD_DEVIATION 17.74 | 66.3 Years STANDARD_DEVIATION 4.16 | 58.2 Years STANDARD_DEVIATION 15.98 |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 0 / 7 | 1 / 3 |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 3 / 7 | 1 / 3 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) and Recommended Dose (RD)
The MTD was defined as the maximum tolerated dose observed after the evaluation of dose limiting toxicity (DLT) in Cycle 1 with 6 participants. If it was judged that the dose was not tolerated and DLT was confirmed in only 3 participants in the lower dose cohort, 3 other participants were to be added and tolerability was evaluated with 6 participants in total. The RD was to be comprehensively determined based on the MTD and safety data. Participants not evaluable for DLT were defined as participants found to be ineligible or in whom DLT evaluation was impossible due to premature termination for reasons other than toxicities in the judgement of the Sponsor, among those who had received at least one dose of the investigational drug after enrollment.
Time frame: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
Population: DLT evaluation analysis set included all participants after excluding, from the Safety Analysis Set, participants who were non-evaluable for DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denileukin Diftitox | Maximum Tolerated Dose (MTD) and Recommended Dose (RD) | 9 ug/kg/day |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf))
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-inf), which was then summarized as the median and full range for all participants and expressed as ng\*min/mL.
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) | 16800 ng*min/mL |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) | 25200 ng*min/mL |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) | 35600 ng*min/mL |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t))
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of AUC(0-t), which was then summarized as the median and full range for all participants and expressed as nanograms\*minutes per milliliter (ng\*min/mL).
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t)) | 10300 ng*min/mL |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t)) | 16900 ng*min/mL |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Area Under the Serum Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC(0-t)) | 18600 ng*min/mL |
Secondary
Maximum Serum Concentration (Cmax) of Denileukin Diftitox
Cmax was defined as the maximum observed concentration of denileukin diftitox following administration of study treatment on Cycle 1 Day 1 and was obtained directly from the measured serum concentration-time curves. Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a lower limit of quantitation (LLOQ) of 30 nanograms per milliliter (ng/mL). Serum pharmacokinetic (PK) data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Cmax, which was then summarized as the median and full range for all participants and expressed as ng/mL.
Time frame: Cycle 1 (Day 1)
Population: PK analysis set included all participants in whom at least one PK parameter could be calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Maximum Serum Concentration (Cmax) of Denileukin Diftitox | 129 ng/mL |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Maximum Serum Concentration (Cmax) of Denileukin Diftitox | 149 ng/mL |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Maximum Serum Concentration (Cmax) of Denileukin Diftitox | 181 ng/mL |
Secondary
Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox
Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, blood coagulation, blood chemistry, and urinalysis values; periodic measurement of vital signs, body weight, 12-lead electrocardiograms (ECGs), Eastern Cooperative Oncology Group performance status, physical examination findings, and ophthalmological examination findings. TEAEs were defined as an AE that had an onset date, or worsening in severity from baseline (pre-treatment), on or after the first dose of study drug up to the last assessment. Treatment-related TEAEs included TEAEs that were considered by the investigator to be possibly or probably related to study drug. SAEs were defined as any untoward medical occurrence which results in death, was life-threatening, required hospitalization or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or caused a congenital anomaly/birth defect.
Time frame: From date of first dose up to 30 days after the last dose of study treatment, up to approximately 4 years 2 months
Population: Safety Analysis Set (SAS) included all participants who received at least one dose of the study drug with at least one evaluable, post-baseline safety datum.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | TEAEs | 3 Participants |
| Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Treatment-related TEAEs | 3 Participants |
| Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Treatment-emergent SAEs | 1 Participants |
| Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Death | 0 Participants |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Death | 0 Participants |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | TEAEs | 7 Participants |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Treatment-emergent SAEs | 3 Participants |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Treatment-related TEAEs | 7 Participants |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Death | 1 Participants |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Treatment-related TEAEs | 3 Participants |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | Treatment-emergent SAEs | 1 Participants |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Number of Participants With Non-Serious Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Denileukin Diftitox | TEAEs | 3 Participants |
Secondary
Recommended Dose
This endpoint was combined with primary outcome measure, MTD
Time frame: For each dose, first dose of study drug (Cycle 1 Day 1) to end of Cycle 1 (Day 21) (1 cycle = 3 weeks)
Population: This endpoint was combined with primary outcome measure, MTD
Secondary
Terminal Elimination Phase Half-life (t1/2)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of t1/2, which was then summarized as the median and full range for all participants and expressed in minutes.
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Terminal Elimination Phase Half-life (t1/2) | 92.9 Minutes |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Terminal Elimination Phase Half-life (t1/2) | 67.8 Minutes |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Terminal Elimination Phase Half-life (t1/2) | 87.4 Minutes |
Secondary
Terminal Phase Rate Constant (λz)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of λz, which was then summarized as the median and full range for all participants and expressed in 1/minutes.
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Terminal Phase Rate Constant (λz) | 0.00746 1/minutes |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Terminal Phase Rate Constant (λz) | 0.0103 1/minutes |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Terminal Phase Rate Constant (λz) | 0.00793 1/minutes |
Secondary
Time to Cmax (Tmax) of Denileukin Diftitox in Serum
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Tmax, which was then summarized as the median and full range for all participants and expressed in minutes.
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Time to Cmax (Tmax) of Denileukin Diftitox in Serum | 64.000 Minutes |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Time to Cmax (Tmax) of Denileukin Diftitox in Serum | 64.000 Minutes |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Time to Cmax (Tmax) of Denileukin Diftitox in Serum | 74.500 Minutes |
Secondary
Total Clearance (CL)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. SerumPK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of CL, which was then summarized as the median and full range for all participants and expressed as milliliters/minutes/kilograms (mL/min/kg).
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Total Clearance (CL) | 0.404 mL/min/kg |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Total Clearance (CL) | 0.361 mL/min/kg |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Total Clearance (CL) | 0.393 mL/min/kg |
Secondary
Volume of Distribution at Steady State (Vss)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vss, which was then summarized as the median and full range for all participants and expressed as mL/kg.
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Volume of Distribution at Steady State (Vss) | 59.8 mL/kg |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Volume of Distribution at Steady State (Vss) | 48.4 mL/kg |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Volume of Distribution at Steady State (Vss) | 54.1 mL/kg |
Secondary
Volume of Distribution at Terminal Phase (Vz)
Blood samples were collected before and 30 minutes after the start of infusion and immediately (0 minutes), 30, 60, 90, and 120 minutes after the end of infusion of denileukin diftitox. The samples were analyzed for the amount of denileukin diftitox in the serum using a validated ligand-binding assay with a LLOQ of 30 ng/mL. Serum PK data were analyzed using a non-compartmental analysis approach to obtain individual participant estimates of Vz, which was then summarized as the median and full range for all participants and expressed as milliliters per kilogram (mL/kg).
Time frame: Cycle 1 (Day 1)
Population: PK analysis set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Denileukin Diftitox | Volume of Distribution at Terminal Phase (Vz) | 54.2 mL/kg |
| Cohort 2: 9 ug/kg/Day Denileukin Diftitox | Volume of Distribution at Terminal Phase (Vz) | 45.2 mL/kg |
| Cohort 3: 12 ug/kg/Day Denileukin Diftitox | Volume of Distribution at Terminal Phase (Vz) | 49.5 mL/kg |