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The purpose of the study was to assess efficacy, tolerability, safety and pharmacokinetics of Romidepsin in subjects with progressive or relapsed peripheral T-cell lymphoma
This is a Phase 1/2, non-randomized, open-label, single-arm trial with two phases. The first phase is a 3 + 3 dose escalation phase to determine a recommended dose for treating patients with Peripheral T-Cell Lymphoma (PTCL) or Cutaneous T-Cell Lymphoma (CTCL) based on the assessment of Dose Limiting Toxicities (DLTs).The second phase will assess efficacy at the recommended dose by measuring objective response [Complete Response (CR), Unconfirmed Complete Response (CR(u)) or Partial Response (PR)] and determining best overall response of each patient. Phase 1 will enroll a maximum of 12 patients and Phase 2 will enroll up to approximately 40 patients
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Romidepsin | Experimental | Patients will receive romidepsin intravenously for 4 hours on Days 1, 8, and 15 of each 28-day cycle until when/if a discontinuation criterion, e.g., disease progression, severe adverse events, or consent withdrawal. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Romidepsin | Drug | Intravenous dosing for 4 hours on Days 1, 8, and 15 of each 28-day cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-limiting Toxicity (DLT) in Accordance With National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 as Determined by the Efficacy and Safety Evaluation Committee (ESEC) | DLT was defined as an adverse event (AE) occurring in Cycle 1 in Phase 1 and judged that the causal relationship to the investigational product could not be denied. The severity of all AEs was graded based upon the NCI CTCAE version 3.0. DLTs were defined as: • Grade 4 Hemoglobin <6.5 g/dL • Grade 4 Neutrophil <500/μL continuing for at least 5 days • Febrile neutropenia (Grade 4 neutropenia caused by fever and ≥ 38.5° C for more than 1 hour) • Grade 4 thrombocyte (< 25,000/μL), or thrombocytopenia with hemorrhage requiring platelet transfusion • Nausea, vomiting, or diarrhea at > grade 3 in spite of treatment • Grade 3 ALT (alanine aminotransferase) or AST (aspartate aminotransferase) values continued for 7 days. • Grade 4 ALT or AST • Grade 2 arrhythmia • Grade 4 non-hematological AEs • Other grade 3 non-hematological AEs except transient fatigue, anorexia, hyponatremia, and tumor lysis syndrome • Other AEs leading to discontinuation of administration | Up to Day 28; Cycle 1 |
| Percentage of PTCL Participants With an Overall Best Response in Accordance With a Modified International Workshop Response Criteria (IWC) 1999 in Phase 2 | Objective disease response in PTCL was defined as patients with a complete response (CR), unconfirmed complete response (CRu) or a partial response (PR) according to modified IWC 1999 criteria and assessed by an independent efficacy reviewer. A CR is >75% decrease in size of maximum 6 largest target within nodal and extranodal lesions, complete disappearance of other nodal and extranodal; total disappearance of clinical disease; disease-related signs and symptoms, normalization of biochemical abnormalities, disappearance of spleen, liver, or kidney enlargement; no bone marrow (BM) involvement, no new sites of disease. CRu: all above criteria fulfilled except for BM involvement is indeterminate. PR: a ≥50% decrease in size of 6 largest target lesions and no increase other nodal and extranodal; no progression of clinical disease; disease-related signs and symptoms, normalization or biochemical abnormalities, no progression in size of liver, spleen, or kidney; and no new sites of disease | Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Measure | Description | Time Frame |
|---|---|---|
| Participants With Treatment-Emergent Adverse Events (TEAEs) Associated With Romidepsin | An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. An AE that resulted in any of the outcomes was defined as a serious (SAE): • Death • Life-threatening event • An inpatient hospitalization or prolongation of existing hospitalization • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect • Other important medical event The investigator judged the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide an explanation for the event. The severity of an AE was evaluated by the investigator according to Common Terminology Criteria for Adverse Events (CTCAE Version 3.0), Japanese Clinical Oncology Group (JCOG) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. |
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Inclusion Criteria:
Patients must fulfill all of the following criteria to be eligible for study participation and have:
Histologically confirmed Peripheral T cell Lymphoma (PTCL) Not Otherwise Specified (NOS), Angioimmunoblastic T-cell Lymphoma, enteropathy- type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous T-cell lymphoma (excludes mycosis fungoides or Sezary syndrome) , hepatosplenic T-cell lymphoma, Anaplastic Large cell lymphoma (ALCL) [anaplastic lymphoma kinase-1 (ALK-1) negative], patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after Autologous Stem-Cell Transplantation, Transformed mycosis fungoides (MF), or Sézary syndrome (SS);
Hemoglobin ≥8.0 g/dL (The value after the 7th day of transfusion)
Absolute neutrophil count (ANC) ≥1.0×10^9/L (The value after the 7th day of G-CSF)
Platelet counts ≥100 x 10^9/L, or, if bone marrow infiltration is recognized, ≥75 ×10^9/L
Total bilirubin (Total-Bil) ≤2 x upper limit of normal (ULN) (≤3.0 x ULN in the presence of demonstrable liver metastasis)
Aspartate Aminotransferase (AST)/Serum Glutamic-Oxaloacetic Transaminase (SGOT) ≤2 x Upper Limit Normal (ULN) (≤3.0 x ULN in the presence of demonstrable liver metastasis)
Alanine Aminotransferase (ALT)/Serum Glutamic-Oxaloacetic Transaminase (SGOT) ≤2 x ULN (≤3.0 x ULN in the presence of demonstrable liver metastasis)
Serum creatinine ≤ 2 x ULN
Exclusion Criteria: Confirmation should be made before enrollment, and the subjects corresponding to the criteria should not be enrolled.
Subjects in whom central nervous lymphoma is recognized during the screening period (If brain metastasis is suspected clinically, CT should be performed.)
Subjects undergoing chemotherapy or immunotherapy for the purpose of treatment of the target disease within 22 days before C1D1 (including C1D1) (using antibody drugs only within 3 months before C1D1)
Subjects receiving local application of steroids within 15 days before C1D1 (including C1D1) Use of steroids for the purpose other than that of treatment of the target disease should be allowed (Only CTCL subjects)
Subjects receiving systemic application of steroids within 22 days before C1D1 (including C1D1) (It is acceptable to continue the use of the steroid for the purpose of treatment of the target disease,which administered in doses ≤ 10mg/day prednisolone or equivalent dose of other glucocorticoid. However increase of steroid dose cannot be allowed during the study period)
Subjects undergoing radiation therapy, PUVA therapy or TSEB for the purpose of treatment of the target disease within 22 days before C1D1 (including C1D1)
Subjects using other investigational products within 22 days before C1D1 (including C1D1) (using antibody drugs only within 3 months before C1D1)
Subjects undergoing blood transfusion and using G-CSF within 8 days before C1D1 (including C1D1)
Subjects with the following abnormalities in the cardiac function
Concomitant use of a drug which may induce significant QT prolongation (refer to 9.2. Prohibited Concomitant Medications and Procedures.)
Concomitant use of strong or moderate CYP3A4 inhibitors which include grapefruit juice
Concomitant use of CYP3A4 inducers which include St John's Wort (1st step only)
Concomitant use of therapeutic warfarin which has a potential drug interaction. Use of a small dose of warfarin or other anticoagulant agent to maintain patency of venous access port and cannulas is permitted.
Clinically important active infections
Known infection with human immunodeficiency virus (HIV) antibody positive, HBs antigen positive or HCV antibody positive. If negative for HBsAg but HBcAb and/or HBsAb positive status, a HBV DNA test will be performed and if positive the subject will be excluded.
Subjects undergoing a wide range of radiation therapy in ≥30% of the bone marrow (such as all parts of the pelvic area or a half of the spinal cord) in the past. The subjects undergoing systemic radiation (including systemic electron therapy) as previous treatment for ASCT will be excluded.
Subjects undergoing a surgery within 15 days before C1D1 (including C1D1); however, even if more than 15 days have passed since the surgery, subjects without evidence of wound healing will be excluded.
Subjects who are during recovery process from severe wound or fracture.
Subjects with a history of allogeneic stem cell transplantation
Patients who are breast-feed during period of the IP administration or within 28 days after the end of the IP administration.
Subjects with a history of any other malignant tumor or solid cancer within previous 3 years (excluding basal or squamous cell carcinoma of skin, and in situ carcinoma of the cervix (CIN3) that has been treated curatively)
Subject with a history of hematological malignant tumor (other than T-cell lymphoma)
Subjects for whom transfusion of red blood cells or platelets is impossible (such as clinical state and religious beliefs)
Significant medical or psychiatric situation by which all of the study procedures may not be observed
Subjects receiving romidepsin in the past (Other HDAC inhibitors are acceptable)
Subjects judged to be inappropriate for this study by the investigator or sub-investigator.
Concomitant use of rifampicin.
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| Name | Affiliation | Role |
|---|---|---|
| Toru Sasaki | Celgene K.K. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nagoya Daini Red Cross Hospital | Nagoya | Aichi-ken | 466-8650 | Japan | ||
| Nagoya City University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28664499 | Derived | Maruyama D, Tobinai K, Ogura M, Uchida T, Hatake K, Taniwaki M, Ando K, Tsukasaki K, Ishida T, Kobayashi N, Ishizawa K, Tatsumi Y, Kato K, Kiguchi T, Ikezoe T, Laille E, Ro T, Tamakoshi H, Sakurai S, Ohtsu T. Romidepsin in Japanese patients with relapsed or refractory peripheral T-cell lymphoma: a phase I/II and pharmacokinetics study. Int J Hematol. 2017 Nov;106(5):655-665. doi: 10.1007/s12185-017-2286-1. Epub 2017 Jun 29. |
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Those with relapsed, recurring or refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) were enrolled in the Phase 1 part of this study. In Phase 2, the target disease was relapsed, recurring or refractory PTCL only. Results are reported up to the data cut-off of 28 July 2015.
This was a Phase 1/2 open-label dose-escalation study. Phase 1 part composed of Cohort 1 (9mg/m^2) and Cohort 2 (14mg/m^2). Japanese participants were enrolled in order from Cohort 1. The dose used in the Phase 2 part was determined based on the frequency of dose limiting toxicities in Phase 1.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1: Romidepsin 9mg/m^2 | Romidepsin 9mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle |
| FG001 | Phase 1: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1 (First Step) |
|
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| Day 1 of study drug through 30 days after the last dose of study drug or discontinuation date; Up to data cut-off of 28 July 2015; maximum follow up time was 184.3 weeks |
| Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Romidepsin in Phase 1 | Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Romidepsin in Phase 1 | Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC∞) of romidepsin on Day 1; if possible the area under the concentration-time curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity was calculated according to the following equation: AUC∞ = AUCt + (Ct/ λz ), where Ct is the last quantifiable concentration. | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 1 | The maximum observed plasma concentration of romidepsin (Cmax) obtained directly from the observed concentration versus time data | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Time to Maximum Plasma Concentration of Romidepsin (Tmax) in Phase 1 | The time to first maximum observed plasma concentration of romidepsin after a single dose on Day 1. | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Terminal Phase Half-life of Romidepsin (t½) in Phase 1 | The terminal phase half-life of romidepsin after a single dose on Day 1, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant. | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. |
| Apparent Total Clearance of Romidepsin (CL/F) of Romidepsin in Phase 1 | The apparent total clearance of romidepsin after a single dose on Day 1, calculated as dose/AUC0-infinity. | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. |
| Apparent Volume of Distribution (Vz/F) of Romidepsin in Phase 1 | Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| AUC0-t, at Steady State (ss) of Romidepsin in Phase 1 at Cycle 1, Day 15 | Area under the plasma concentration-time curve from time zero to the last quantifiable time point at steady state, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Cmax, ss of Romidepsin in Phase 1 at Cycle 1, Day 15 | Maximum observed concentration in plasma at steady state | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Tmax,ss of Romidepsin in Phase 1 at Cycle 1, Day 15 | Observed time to first maximum plasma concentration at steady state | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Terminal Phase Half-life of Romidepsin (t½) in Phase 1 at Cycle 1, Day 15 | The terminal phase half-life of romidepsin after a single dose on Day 15, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant. | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. |
| AUC0-t, Accumulation Ratio of Romidepsin in Phase 1, Cycle 1 | Area under the plasma concentration-time curve from time zero to the last quantifiable time point; accumulation ratio calculated as AUC (0-t),ss/AUC (0-t) | Day 1 and Day 15 in Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
| Cmax Accumulation Ratio of Romidepsin in Phase 1, Cycle 1 | Cmax of Romidepsin: accumulation ratio based on Cmax calculated as Cmax,ss/Cmax | Day 1 and Day 15 in Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at end of administration) hours after the start of administration, 0.25, 0.5, 1, 2, 4, 6, 20, and 44 hours after the end of administration. Day 8, Cycle 1, samples collected at 0 hour |
| The Percentage of Participants With Abnormal Q-wave and T Wave Intervals | The time from the start of the Q-wave to the end of the T-wave QTc intervals greater than 450 msec post-baseline performed by centralized reviewer. The Bazett's (QTcB) and Fridericia (QTcF) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval | Median follow-up: 100 days; up to data cut-off of 28 July 2015 |
| Percentage of PTCL Participants With the Best Response in Accordance With the Modified 2007 International Workshop Response Criteria as Assessed by IER | Objective disease response in PTCL was defined as achieving a CR or PR based on the Modified 2007 IWC. A CR = a complete disappearance of all disease; lymph node mass regression to normal size on computerized tomography (CT) scan or negative on positron emission tomography (PET); non-palpable splenic and disappearance of liver nodules; infiltrate cleared on repeat bone marrow (BM), immunohistochemistry negative. PR = a reduction of measurable lesions; ≥ 50% decrease in sum of the products of the greatest diameters (SPD) of up to 6 largest dominant masses, no enlargement in size of other nodes; ≥ 50% decrease in SPD and no increase in liver or spleen. | Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 1999 IWC as Assessed by IER | TTR for PTCL was defined as the time in days from first dose date to the first date of objective disease response. | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 2007 IWC as Assessed by IER | TTR for PTCL was defined as the time in days from first dose date to the first date of objective disease response. | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 1999 IWC as Assessed by the IER. | DOR was defined as the number of days from the date of the first disease response (Complete, Unconfirmed Complete or Partial Response) until the date of progression, analyzed using Kaplan-Meier methods. | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 2007 IWC as Assessed by the IER. | DOR was defined as the number of days from the date of the first disease response (Complete, Unconfirmed Complete or Partial Response) until the date of progression, analyzed using Kaplan-Meier methods. | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Kaplan Meier Estimate of Time to Progression (TTP) in PTCL Participants Based on the 1999 IWC as Assessed by IER | Time to progression (≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions) was defined as the duration from the date of the first study drug dose to the date of relapse or progression | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Kaplan Meier (K-M) Estimate of Time to Progression (TTP) in PTCL Participants Based on the Modified 2007 IWC as Assessed by IER | Time to progression (≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions) was defined as the duration from the date of the first study drug dose to the date of relapse or progression | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
| Nagoya |
| Aichi-ken |
| 467-8602 |
| Japan |
| National Cancer Center Hospital East | Kashiwa | Chiba | 277-8577: | Japan |
| Ehime University Hospital | Tōon | Ehime | 791-0295 | Japan |
| Chugoku Central Hospital | Fukuyamashi | Hiroshima | 720-0001 | Japan |
| Sapporo Hokuyu Hospital | Sapporo | Hokkaido | 003-0006 | Japan |
| Sapporo Medical University Hospital | Sapporo | Hokkaido | 060-8543 | Japan |
| Tokai University School of Medicine | Isehara | Kanagawa | 259-1193 | Japan |
| Kochi Medical School Hospital | Nankoku | Kochi | 783-8505 | Japan |
| Kinki University Hospital | Sayama | Osaka | 589-8511 | Japan |
| National Cancer Center Hospital | Chūō | Tokyo | 104-0045 | Japan |
| Japanese Red Cross Medical Center | Shibuya City | Tokyo | 150-8935 | Japan |
| Kyushu University Hospital | Fukuoka | 812-8582 | Japan |
| Kumamoto University Hospital | Kumamoto | 860-8556 | Japan |
| University hospital, Kyoto prefectural University of Medicine | Kyoto | 602-8566 | Japan |
| Tohoku University Hospital | Miyagi | 980-8574 | Japan |
| The Cancer Institute Hospital of JFCR | Tokyo | 135-8550 | Japan |
| FG002 | Phase 2: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| COMPLETED |
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| NOT COMPLETED |
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| Phase 2 (Second Step) |
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Intent to Treat (ITT) includes all participants who received at least one dose of romidepsin.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1: Romidepsin 9mg/m^2 | Romidepsin 9mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle |
| BG001 | Phase 1: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| BG002 | Phase 2: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Number | participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Disease Type by Investigator | PTCL is included in a heterogenous group of rare diseases resulting from clonal proliferation of mature thymic lymphocytes. These T-cell tumors account for about 10% to 15% of all lymphoid tumors. CTCL is a non-Hodgkin's lymphoma of helper T-cells that usually presents in the skin. It is classified mainly into mycosis fungoides and Sézary syndrome, and the stage is classified by the Tumor Node Metastasis Blood (TNMB) classification. | Number | participants |
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| Eastern Cooperative Oncology Group (ECOG) | Eastern Cooperative Oncology Group (ECOG) performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active (Most Favorable Activity); 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, No self-care (Least Favorable Activity) | Number | participants |
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| Body Surface Area (BSA) | BSA is the total surface area of the body and was used to calculate the dosage for romidepsin. | Mean | Standard Deviation | m2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| Primary | Number of Participants With Dose-limiting Toxicity (DLT) in Accordance With National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 as Determined by the Efficacy and Safety Evaluation Committee (ESEC) | DLT was defined as an adverse event (AE) occurring in Cycle 1 in Phase 1 and judged that the causal relationship to the investigational product could not be denied. The severity of all AEs was graded based upon the NCI CTCAE version 3.0. DLTs were defined as: • Grade 4 Hemoglobin <6.5 g/dL • Grade 4 Neutrophil <500/μL continuing for at least 5 days • Febrile neutropenia (Grade 4 neutropenia caused by fever and ≥ 38.5° C for more than 1 hour) • Grade 4 thrombocyte (< 25,000/μL), or thrombocytopenia with hemorrhage requiring platelet transfusion • Nausea, vomiting, or diarrhea at > grade 3 in spite of treatment • Grade 3 ALT (alanine aminotransferase) or AST (aspartate aminotransferase) values continued for 7 days. • Grade 4 ALT or AST • Grade 2 arrhythmia • Grade 4 non-hematological AEs • Other grade 3 non-hematological AEs except transient fatigue, anorexia, hyponatremia, and tumor lysis syndrome • Other AEs leading to discontinuation of administration | DLT population included all participants in the Phase 1 portion who received at least one dose of romidepsin. Of 8 participants enrolled in the 14mg/m^2 cohort, 2 participants, one with a critical Good Clinical Practice (GCP)violation and the other who did not complete Cycle 1 due to consent withdrawal, were excluded from the DLT assessment. | Posted | Number | participants | Up to Day 28; Cycle 1 |
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| Primary | Percentage of PTCL Participants With an Overall Best Response in Accordance With a Modified International Workshop Response Criteria (IWC) 1999 in Phase 2 | Objective disease response in PTCL was defined as patients with a complete response (CR), unconfirmed complete response (CRu) or a partial response (PR) according to modified IWC 1999 criteria and assessed by an independent efficacy reviewer. A CR is >75% decrease in size of maximum 6 largest target within nodal and extranodal lesions, complete disappearance of other nodal and extranodal; total disappearance of clinical disease; disease-related signs and symptoms, normalization of biochemical abnormalities, disappearance of spleen, liver, or kidney enlargement; no bone marrow (BM) involvement, no new sites of disease. CRu: all above criteria fulfilled except for BM involvement is indeterminate. PR: a ≥50% decrease in size of 6 largest target lesions and no increase other nodal and extranodal; no progression of clinical disease; disease-related signs and symptoms, normalization or biochemical abnormalities, no progression in size of liver, spleen, or kidney; and no new sites of disease | Intent to treat population for participants with PTCL who received at least one dose of Romidepsin | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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| Secondary | Participants With Treatment-Emergent Adverse Events (TEAEs) Associated With Romidepsin | An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. An AE that resulted in any of the outcomes was defined as a serious (SAE): • Death • Life-threatening event • An inpatient hospitalization or prolongation of existing hospitalization • Persistent or significant disability or incapacity; • Congenital anomaly or birth defect • Other important medical event The investigator judged the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide an explanation for the event. The severity of an AE was evaluated by the investigator according to Common Terminology Criteria for Adverse Events (CTCAE Version 3.0), Japanese Clinical Oncology Group (JCOG) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. | Safety population includes all participants who received at least one dose of romidepsin | Posted | Number | participants | Day 1 of study drug through 30 days after the last dose of study drug or discontinuation date; Up to data cut-off of 28 July 2015; maximum follow up time was 184.3 weeks |
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| Secondary | Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Romidepsin in Phase 1 | Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing. | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Romidepsin in Phase 1 | Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC∞) of romidepsin on Day 1; if possible the area under the concentration-time curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity was calculated according to the following equation: AUC∞ = AUCt + (Ct/ λz ), where Ct is the last quantifiable concentration. | PK Population consisted of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for romidepsin for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 1 | The maximum observed plasma concentration of romidepsin (Cmax) obtained directly from the observed concentration versus time data | Pharmacokinetic (PK) Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | Time to Maximum Plasma Concentration of Romidepsin (Tmax) in Phase 1 | The time to first maximum observed plasma concentration of romidepsin after a single dose on Day 1. | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Median | Full Range | hours | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | Terminal Phase Half-life of Romidepsin (t½) in Phase 1 | The terminal phase half-life of romidepsin after a single dose on Day 1, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant. | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. |
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| Secondary | Apparent Total Clearance of Romidepsin (CL/F) of Romidepsin in Phase 1 | The apparent total clearance of romidepsin after a single dose on Day 1, calculated as dose/AUC0-infinity. | PK population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. |
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| Secondary | Apparent Volume of Distribution (Vz/F) of Romidepsin in Phase 1 | Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | AUC0-t, at Steady State (ss) of Romidepsin in Phase 1 at Cycle 1, Day 15 | Area under the plasma concentration-time curve from time zero to the last quantifiable time point at steady state, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | Cmax, ss of Romidepsin in Phase 1 at Cycle 1, Day 15 | Maximum observed concentration in plasma at steady state | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | Tmax,ss of Romidepsin in Phase 1 at Cycle 1, Day 15 | Observed time to first maximum plasma concentration at steady state | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Median | Full Range | hours | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
|
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| Secondary | Terminal Phase Half-life of Romidepsin (t½) in Phase 1 at Cycle 1, Day 15 | The terminal phase half-life of romidepsin after a single dose on Day 15, calculated according to the following equation: t½ = 0.693/λz, where λz is the terminal phase rate constant. | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Day 15 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration. |
|
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| Secondary | AUC0-t, Accumulation Ratio of Romidepsin in Phase 1, Cycle 1 | Area under the plasma concentration-time curve from time zero to the last quantifiable time point; accumulation ratio calculated as AUC (0-t),ss/AUC (0-t) | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Day 1 and Day 15 in Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration |
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| Secondary | Cmax Accumulation Ratio of Romidepsin in Phase 1, Cycle 1 | Cmax of Romidepsin: accumulation ratio based on Cmax calculated as Cmax,ss/Cmax | PK Population includes of all participants who had sufficient concentration-time data to enable the calculation of PK parameters for at least one PK day. For those who were determined to be noncompliant to receiving romidepsin, or for those with incomplete data, a decision to include the analysis was made on a case-by-case basis. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Day 1 and Day 15 in Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at end of administration) hours after the start of administration, 0.25, 0.5, 1, 2, 4, 6, 20, and 44 hours after the end of administration. Day 8, Cycle 1, samples collected at 0 hour |
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| Secondary | The Percentage of Participants With Abnormal Q-wave and T Wave Intervals | The time from the start of the Q-wave to the end of the T-wave QTc intervals greater than 450 msec post-baseline performed by centralized reviewer. The Bazett's (QTcB) and Fridericia (QTcF) correction were used as the standard clinical correction for calculating the heart rate-corrected QTc interval | The ECG population includes all participants who received romidepsin on Day 1 of Cycle 1 with at least one post-baseline QTc result | Posted | Number | percentage of participants | Median follow-up: 100 days; up to data cut-off of 28 July 2015 |
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| Secondary | Percentage of PTCL Participants With the Best Response in Accordance With the Modified 2007 International Workshop Response Criteria as Assessed by IER | Objective disease response in PTCL was defined as achieving a CR or PR based on the Modified 2007 IWC. A CR = a complete disappearance of all disease; lymph node mass regression to normal size on computerized tomography (CT) scan or negative on positron emission tomography (PET); non-palpable splenic and disappearance of liver nodules; infiltrate cleared on repeat bone marrow (BM), immunohistochemistry negative. PR = a reduction of measurable lesions; ≥ 50% decrease in sum of the products of the greatest diameters (SPD) of up to 6 largest dominant masses, no enlargement in size of other nodes; ≥ 50% decrease in SPD and no increase in liver or spleen. | Intent to treat population for participants with PTCL who received at least one dose of romidepsin | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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| Secondary | Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 1999 IWC as Assessed by IER | TTR for PTCL was defined as the time in days from first dose date to the first date of objective disease response. | Intent to treat population for participants with PTCL who received at least one dose of romidepsin and achieved a PR or better (CR, CRu or PR) | Posted | Median | Full Range | days | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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| Secondary | Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 2007 IWC as Assessed by IER | TTR for PTCL was defined as the time in days from first dose date to the first date of objective disease response. | Intent to treat population for participants with PTCL who received at least one dose of romidepsin and achieved a PR or better (CR, CRu or PR) | Posted | Median | Full Range | days | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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| Secondary | Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 1999 IWC as Assessed by the IER. | DOR was defined as the number of days from the date of the first disease response (Complete, Unconfirmed Complete or Partial Response) until the date of progression, analyzed using Kaplan-Meier methods. | Intent to treat population for participants with PTCL who received at least one dose of romidepsin and achieved a PR or better (CR, CRu or PR) | Posted | Median | 95% Confidence Interval | days | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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| Secondary | Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 2007 IWC as Assessed by the IER. | DOR was defined as the number of days from the date of the first disease response (Complete, Unconfirmed Complete or Partial Response) until the date of progression, analyzed using Kaplan-Meier methods. | Intent to treat population for participants with PTCL who received at least one dose of romidepsin and achieved a PR or better (CR, CRu or PR) | Posted | Median | 95% Confidence Interval | days | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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| Secondary | Kaplan Meier Estimate of Time to Progression (TTP) in PTCL Participants Based on the 1999 IWC as Assessed by IER | Time to progression (≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions) was defined as the duration from the date of the first study drug dose to the date of relapse or progression | ITT includes all participants who received at least one dose of romidepsin | Posted | Median | 95% Confidence Interval | days | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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| Secondary | Kaplan Meier (K-M) Estimate of Time to Progression (TTP) in PTCL Participants Based on the Modified 2007 IWC as Assessed by IER | Time to progression (≥50% increase from the nadir in the individual sum of the products of the diameters of any index lesion; the reappearance of pathology, enlargement of liver/spleen, or unequivocal progression of non-measurable disease or appearance of any new lesions) was defined as the duration from the date of the first study drug dose to the date of relapse or progression | ITT includes all participants who received at least one dose of romidepsin | Posted | Median | 95% Confidence Interval | days | Median follow-up time was 100 days; up to the data cut-off of 28 July 2015 |
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Day 1 of study drug through 30 days after the last dose of study drug or discontinuation date; Up to data cut-off of 28 July 2015; maximum time exposed to study was 1290 days; maximum time on study treatment was 184.3 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1: Romidepsin 9mg/m^2 | Romidepsin 9mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle | 1 | 3 | 3 | 3 | ||
| EG001 | Phase 1: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. | 4 | 7 | 7 | 7 | ||
| EG002 | Phase 2: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. | 10 | 40 | 40 | 40 | ||
| EG003 | Total: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. | 14 | 47 | 47 | 47 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cytomegalovirus infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Bacterial infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumocystis jiroveci pneumonia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cardio-respiratory arrest | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Akathisia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Depressed level of consciousness | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Multi-organ failure | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hyperkalemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Lip dry | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Periodontal disease | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Sensitivity of teeth | Gastrointestinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypothermia | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Blood phosphorus increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Electrocardiogram ST-T change | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Electrocardiogram ST-T segment elevation | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Electrocardiogram T wave inversion | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Renal Function Test abnormal | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Peripheral Sensory neuropathy | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Akathisia | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Carotid arteriosclerosis | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Haemorrhage subcutaneous | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Henoch-Schonlein purpura | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Cytomegalovirus infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Bacterial Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Infected epidermal cyst | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Pneumocystis jiroveci pneumonia | Infections and infestations | MedDRA (14.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Supraventriclar extrasystoles | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Long QT syndrome | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA (14.0) | Systematic Assessment |
| |
| Phlebitis | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Iritis | Eye disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Vitreous Floaters | Eye disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Biliary colic | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Cancer Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (14.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (14.0) | Systematic Assessment |
| |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (14.0) | Systematic Assessment |
|
Disclosure agreements vary; the Investigators shall not disclose any material/information disclosed by the Sponsor (Celgene KK) with the clinical trial or information obtained by conducting the clinical trial to third parties without Sponsor's prior written approval.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anne McClain, Senior Manager, Clinical Trial Disclosure | Celgene Corporation | 888-260-1599 | ClinicalTrialDisclosure@celgene.com |
| ID | Term |
|---|---|
| D016411 | Lymphoma, T-Cell, Peripheral |
| ID | Term |
|---|---|
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C087123 | romidepsin |
Not provided
Not provided
Not provided
| Withdrawal by Subject |
|
| Protocol Violation |
|
| Other |
|
| ≥65 years |
|
| Male |
|
| CTCL |
|
| 1 = (Restrictive but ambulatory) |
|
| 2 = (Ambulatory but unable to work) |
|
| 3 = (Limited self care) |
|
| 4 = (Completely Disabled) |
|
| Phase 1: Romidepsin 14mg/m^2 |
Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| OG002 | Phase 2: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| OG003 | Total: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
|
|
|
Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| OG002 | Phase 2: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| OG003 | Total: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
| Participants |
|
|
|
|
| Participants |
|
|
|
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
|
| Counts |
|---|
| Participants |
|
|
| Participants |
|
|
|
|
Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
|
|
| OG002 |
| Phase 2: Romidepsin 14mg/m^2 |
Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
| OG003 | Total: Romidepsin 14mg/m^2 | Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
|
|
| Participants |
|
|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
| OG003 |
| Total: Romidepsin 14mg/m^2 |
Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
|
|
| OG003 |
| Total: Romidepsin 14mg/m^2 |
Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle. |
|
|