A Japanese Phase 1/2 Study to Assess the Efficacy, Safety and Pharmacokinetics of Romidepsin in Patients With Peripheral T-cell Lymphoma (PTCL)

• ClinicalTrials.gov Identifier: NCT01456039
• Recruitment Status: Completed
• First Posted: October 20, 2011
• Results First Posted: August 19, 2016
• Last Update Posted: February 11, 2019
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma, T-cell, Peripheral
• Intervention: Drug: Romidepsin
• Enrollment: 51

Participant Flow

Recruitment Details	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.
Pre-assignment Details	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.

Arm/Group Title	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2
Arm/Group Description	Romidepsin 9mg/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.	Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle.
Period Title: Phase 1 (First Step)
Started	3	8	0
Completed	1 [1]	1 [1]	0
Not Completed	2	7	0
Reason Not Completed
Disease Progression	1	1	0
Withdrawal by Subject	1	2	0
Adverse Event	0	3	0
Other	0	1	0
[1] Completed = on treatment
Period Title: Phase 2 (Second Step)
Started	0	0	40
Completed	0	0	7
Not Completed	0	0	33
Reason Not Completed
Disease Progression	0	0	17
Adverse Event	0	0	10
Withdrawal by Subject	0	0	4
Protocol Violation	0	0	1
Other	0	0	1

Baseline Characteristics

Arm/Group Title		Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total
Arm/Group Description		Romidepsin 9mg/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.	Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle.	Total of all reporting groups
Overall Number of Baseline Participants		3	7	40	50
Baseline Analysis Population Description		Intent to Treat (ITT) includes all participants who received at least one dose of romidepsin.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	3 participants	7 participants	40 participants	50 participants
		59.0 (9.54)	73.6 (4.20)	68.5 (8.43)	68.7 (8.47)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3 participants	7 participants	40 participants	50 participants
<65 years		2	0	12	14
≥65 years		1	7	28	36
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	7 participants	40 participants	50 participants
	Female	2 66.7%	2 28.6%	17 42.5%	21 42.0%
	Male	1 33.3%	5 71.4%	23 57.5%	29 58.0%
Disease Type by Investigator [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3 participants	7 participants	40 participants	50 participants
PTCL		2	6	40	48
CTCL		1	1	0	2
		[1] Measure Description: 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.
Eastern Cooperative Oncology Group (ECOG) [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	3 participants	7 participants	40 participants	50 participants
0 = (Fully Active)		0	4	22	26
1 = (Restrictive but ambulatory)		1	2	14	17
2 = (Ambulatory but unable to work)		2	1	4	7
3 = (Limited self care)		0	0	0	0
4 = (Completely Disabled)		0	0	0	0
		[1] Measure Description: 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)
Body Surface Area (BSA) [1]; Mean (Standard Deviation); Unit of measure: M2
	Number Analyzed	3 participants	7 participants	40 participants	50 participants
		1.640 (0.1114)	1.563 (0.2034)	1.554 (0.1768)	1.561 (0.1757)
		[1] Measure Description: BSA is the total surface area of the body and was used to calculate the dosage for romidepsin.

Outcome Measures

1. Primary Outcome

Title	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)
Description	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
Time Frame	Up to Day 28; Cycle 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	6
Measure Type: Number; Unit of Measure: participants
	0	0

2. Primary Outcome

Title	Percentage of PTCL Participants With an Overall Best Response in Accordance With a Modified International Workshop Response Criteria (IWC) 1999 in Phase 2
Description	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
Time Frame	Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

Intent to treat population for participants with PTCL who received at least one dose of Romidepsin

Arm/Group Title	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.	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.
Overall Number of Participants Analyzed	2	6	40	46
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0; (0.000 to 0.000)	66.7; (28.947 to 100.000)	42.5; (27.180 to 57.820)	45.7; (31.258 to 60.046)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phase 2: Romidepsin 14mg/m^2
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Based on one sample binomial test for dichotomized response proportion against the null hypothesis ( H0 p≤0.1)
	Method	Binomial test for dichotomized response
	Comments	[Not Specified]

3. Secondary Outcome

Title	Participants With Treatment-Emergent Adverse Events (TEAEs) Associated With Romidepsin
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Safety population includes all participants who received at least one dose of romidepsin

Arm/Group Title	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.	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.
Overall Number of Participants Analyzed	3	7	40	47
Measure Type: Number; Unit of Measure: participants
Any 1 TEAE	3	7	40	47
TEAE related to any study drug	3	7	40	47
TEAE with CTCAE Grade 3 or greater	3	6	37	43
TEAE with CTCAE ≥Grade 3 related to study drug	3	6	37	43
≥ 1 serious TEAE	1	4	10	14
Serious TEAE related to study drug	0	4	6	10
TEAE leading to discontinuation of study drug	0	3	10	13
TEAE related leading to discontinuation of drug	0	3	9	12
TEAE leading to dose held of study drug	1	4	24	28
Related TEAE leading to dose held of study drug	1	3	22	25
TEAE leading to dose reduction of study drug	0	4	17	21
Related TEAE leading to dose reduction of drug	0	4	17	21
TEAE leading to dose interruption of study drug	1	4	23	27
Related TEAE leading to dose interruption of drug	1	3	22	25
At least one TEAE with NCI CTCAE Grade 5	0	0	2	2

4. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Romidepsin in Phase 1
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
	1023.76; (66.7%)	2325.55; (35.3%)

5. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Romidepsin in Phase 1
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
	1027.08; (66.6%)	2330.91; (35.2%)

6. Secondary Outcome

Title	Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 1
Description	The maximum observed plasma concentration of romidepsin (Cmax) obtained directly from the observed concentration versus time data
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	269.75; (48.9%)	593.47; (37.2%)

7. Secondary Outcome

Title	Time to Maximum Plasma Concentration of Romidepsin (Tmax) in Phase 1
Description	The time to first maximum observed plasma concentration of romidepsin after a single dose on Day 1.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	7
Median (Full Range); Unit of Measure: hours
	4.02; (1.9 to 4.02)	2.00; (1.00 to 4.1)

8. Secondary Outcome

Title	Terminal Phase Half-life of Romidepsin (t½) in Phase 1
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	9.52; (19.8%)	9.12; (11.6%)

9. Secondary Outcome

Title	Apparent Total Clearance of Romidepsin (CL/F) of Romidepsin in Phase 1
Description	The apparent total clearance of romidepsin after a single dose on Day 1, calculated as dose/AUC0-infinity.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: L/h
	14.29; (60.8%)	9.31; (35.4%)

10. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F) of Romidepsin in Phase 1
Description	Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	7
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Liters
	196.24; (86.8%)	122.47; (40.4%)

11. Secondary Outcome

Title	AUC0-t, at Steady State (ss) of Romidepsin in Phase 1 at Cycle 1, Day 15
Description	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
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng*h/mL
	1024.66; (78.1%)	1825.74; (25.8%)

12. Secondary Outcome

Title	Cmax, ss of Romidepsin in Phase 1 at Cycle 1, Day 15
Description	Maximum observed concentration in plasma at steady state
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ng/mL
	250.05; (63.3%)	489.47; (31.2%)

13. Secondary Outcome

Title	Tmax,ss of Romidepsin in Phase 1 at Cycle 1, Day 15
Description	Observed time to first maximum plasma concentration at steady state
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	6
Median (Full Range); Unit of Measure: hours
	1.95; (1.9 to 3.9)	2.94; (1.0 to 4.3)

14. Secondary Outcome

Title	Terminal Phase Half-life of Romidepsin (t½) in Phase 1 at Cycle 1, Day 15
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hours
	8.77; (18.6%)	9.01; (15.8%)

15. Secondary Outcome

Title	AUC0-t, Accumulation Ratio of Romidepsin in Phase 1, Cycle 1
Description	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)
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ratio
	1.00; (19.6%)	0.83; (24.3%)

16. Secondary Outcome

Title	Cmax Accumulation Ratio of Romidepsin in Phase 1, Cycle 1
Description	Cmax of Romidepsin: accumulation ratio based on Cmax calculated as Cmax,ss/Cmax
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.
Overall Number of Participants Analyzed	3	6
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ratio
	0.93; (15.3%)	0.86; (22.2%)

17. Secondary Outcome

Title	The Percentage of Participants With Abnormal Q-wave and T Wave Intervals
Description	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
Time Frame	Median follow-up: 100 days; up to data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

The ECG population includes all participants who received romidepsin on Day 1 of Cycle 1 with at least one post-baseline QTc result

Arm/Group Title	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.	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.
Overall Number of Participants Analyzed	3	7	40	47
Measure Type: Number; Unit of Measure: percentage of participants
QTcB >450 msec	100	57.1	55.0	55.3
QTcB >480 msec	66.7	28.6	0.0	4.3
QTcB >500 msec	33.3	14.3	0.0	2.1
QTcB increase from predose >30 msec	66.7	57.1	10.0	17.0
QTcB increase from predose >60 msec	33.3	28.6	0.0	4.3
QTcF >450 msec	33.3	14.3	10.0	10.6
QTcF >480 msec	33.3	14.3	0.0	2.1
QTcF >500 msec	33.3	14.3	0.0	2.1
QTcF increase from predose >30 msec	66.7	57.1	10.0	17.0
QTcF increase from predose >60 msec	33.3	14.3	0.0	2.1

18. Secondary Outcome

Title	Percentage of PTCL Participants With the Best Response in Accordance With the Modified 2007 International Workshop Response Criteria as Assessed by IER
Description	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.
Time Frame	Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

Intent to treat population for participants with PTCL who received at least one dose of romidepsin

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.	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.
Overall Number of Participants Analyzed	2	6	40	46
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0; (0.000 to 0.000)	16.7; (0.000 to 46.487)	42.5; (27.180 to 57.820)	39.1; (25.027 to 53.234)

19. Secondary Outcome

Title	Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 1999 IWC as Assessed by IER
Description	TTR for PTCL was defined as the time in days from first dose date to the first date of objective disease response.
Time Frame	Median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	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.	Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle.
Overall Number of Participants Analyzed	4	17	21
Median (Full Range); Unit of Measure: days
	109.0; (51.0 to 812.0)	56.0; (49.0 to 71.0)	56.0; (49.0 to 812.0)

20. Secondary Outcome

Title	Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 2007 IWC as Assessed by IER
Description	TTR for PTCL was defined as the time in days from first dose date to the first date of objective disease response.
Time Frame	Median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	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.	Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle.
Overall Number of Participants Analyzed	1	17	18
Median (Full Range); Unit of Measure: days
	737.0; (737.0 to 737.0)	56.0; (50.0 to 71.0)	56.0; (50.0 to 737.0)

21. Secondary Outcome

Title	Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 1999 IWC as Assessed by the IER.
Description	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.
Time Frame	Median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Phase 1: Cohort 2: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	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.	Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle.
Overall Number of Participants Analyzed	4	17	21
Median (95% Confidence Interval); Unit of Measure: days
	106.00; (62.00 to 843.00)	337.00 [1]; (50.00 to NA)	337.00; (62.00 to 843.00)

[1]

Not estimable due to the low number of events

22. Secondary Outcome

Title	Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 2007 IWC as Assessed by the IER.
Description	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.
Time Frame	Median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

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)

Arm/Group Title	Phase 1: Cohort 2: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	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.	Romidepsin 14mg/m^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle.
Overall Number of Participants Analyzed	1	17	18
Median (95% Confidence Interval); Unit of Measure: days
	163.00 [1]; (NA to NA)	337.00 [1]; (60.00 to NA)	163.00 [1]; (60.00 to NA)

[1]

Not available = Not estimable due to the low number of events

23. Secondary Outcome

Title	Kaplan Meier Estimate of Time to Progression (TTP) in PTCL Participants Based on the 1999 IWC as Assessed by IER
Description	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
Time Frame	Median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

ITT includes all participants who received at least one dose of romidepsin

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.	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.
Overall Number of Participants Analyzed	2	6	40	46
Median (95% Confidence Interval); Unit of Measure: days
	114.00 [1]; (NA to NA)	899.00; (112.00 to 899.00)	170.00; (99.00 to 392.00)	179.00; (101.00 to 392.00)

[1]

Not estimable due to the low number of events

24. Secondary Outcome

Title	Kaplan Meier (K-M) Estimate of Time to Progression (TTP) in PTCL Participants Based on the Modified 2007 IWC as Assessed by IER
Description	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
Time Frame	Median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Outcome Measure Data

Analysis Population Description

ITT includes all participants who received at least one dose of romidepsin

Arm/Group Title	Phase 1: Cohort 1: Romidepsin 9mg/m^2	Phase 1: Cohort 2: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description:	Romidepsin 9mg/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.	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.
Overall Number of Participants Analyzed	2	6	40	46
Median (95% Confidence Interval); Unit of Measure: days
	NA [1]; (NA to NA)	899.00 [2]; (NA to NA)	179.00; (96.00 to 392.00)	179.00; (96.00 to 392.00)

[1]

Median time to progression based on K-M estimate had not been reached

[2]

Not estimable due to low number of events

Adverse Events

Time Frame	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
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
Arm/Group Description	Romidepsin 9mg/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.	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.
All-Cause Mortality
	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events
	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	1/3 (33.33%)	4/7 (57.14%)	10/40 (25.00%)	14/47 (29.79%)
Cardiac disorders
Angina pectoris † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Cardiac failure acute † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Cardio-respiratory arrest † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Eye disorders
Retinal detachment † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Gastrointestinal disorders
Gastrointestinal haemorrhage † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
General disorders
Pyrexia † 1	0/3 (0.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Multi-organ failure † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Hepatobiliary disorders
Hepatic function abnormal † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Infections and infestations
Cytomegalovirus infection † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Bacterial infection † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Hepatitis B † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Pneumocystis jiroveci pneumonia † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Pneumonia † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Pneumonia bacterial † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Sepsis † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Urinary tract infection † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Metabolism and nutrition disorders
Dehydration † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Hyperkalemia † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	0/47 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Diffuse large B-cell lymphoma † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Tumour associated fever † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Nervous system disorders
Akathisia † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Altered state of consciousness † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Depressed level of consciousness † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion † 1	0/3 (0.00%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Phase 1: Romidepsin 9mg/m^2	Phase 1: Romidepsin 14mg/m^2	Phase 2: Romidepsin 14mg/m^2	Total: Romidepsin 14mg/m^2
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	3/3 (100.00%)	7/7 (100.00%)	40/40 (100.00%)	47/47 (100.00%)
Blood and lymphatic system disorders
Thrombocytopenia † 1	3/3 (100.00%)	7/7 (100.00%)	39/40 (97.50%)	46/47 (97.87%)
Lymphopenia † 1	3/3 (100.00%)	7/7 (100.00%)	34/40 (85.00%)	41/47 (87.23%)
Leukopenia † 1	3/3 (100.00%)	6/7 (85.71%)	33/40 (82.50%)	39/47 (82.98%)
Neutropenia † 1	3/3 (100.00%)	5/7 (71.43%)	32/40 (80.00%)	37/47 (78.72%)
Anaemia † 1	2/3 (66.67%)	3/7 (42.86%)	12/40 (30.00%)	15/47 (31.91%)
Cardiac disorders
Atrial fibrillation † 1	0/3 (0.00%)	1/7 (14.29%)	3/40 (7.50%)	4/47 (8.51%)
Supraventriclar extrasystoles † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Angina pectoris † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Long QT syndrome † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Pericardial effusion † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Eye disorders
Iritis † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Vitreous Floaters † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Gastrointestinal disorders
Nausea † 1	3/3 (100.00%)	4/7 (57.14%)	20/40 (50.00%)	24/47 (51.06%)
Vomiting † 1	3/3 (100.00%)	3/7 (42.86%)	15/40 (37.50%)	18/47 (38.30%)
Diarrhoea † 1	2/3 (66.67%)	2/7 (28.57%)	14/40 (35.00%)	16/47 (34.04%)
Constipation † 1	0/3 (0.00%)	1/7 (14.29%)	15/40 (37.50%)	16/47 (34.04%)
Stomatitis † 1	0/3 (0.00%)	2/7 (28.57%)	6/40 (15.00%)	8/47 (17.02%)
Abdominal discomfort † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Abdominal pain upper † 1	1/3 (33.33%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Lip dry † 1	2/3 (66.67%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Periodontal disease † 1	0/3 (0.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Dental caries † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Gastritis † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Haemorrhoids † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Sensitivity of teeth † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
General disorders
Pyrexia † 1	3/3 (100.00%)	5/7 (71.43%)	23/40 (57.50%)	28/47 (59.57%)
Fatigue † 1	3/3 (100.00%)	1/7 (14.29%)	12/40 (30.00%)	13/47 (27.66%)
Malaise † 1	0/3 (0.00%)	3/7 (42.86%)	10/40 (25.00%)	13/47 (27.66%)
Injection site reaction † 1	0/3 (0.00%)	2/7 (28.57%)	4/40 (10.00%)	6/47 (12.77%)
Oedema peripheral † 1	1/3 (33.33%)	0/7 (0.00%)	3/40 (7.50%)	3/47 (6.38%)
Chills † 1	0/3 (0.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Face oedema † 1	0/3 (0.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Hypothermia † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Influenza like illness † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Non-cardiac chest pain † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Hepatobiliary disorders
Hepatic function abnormal † 1	0/3 (0.00%)	0/7 (0.00%)	3/40 (7.50%)	3/47 (6.38%)
Biliary colic † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Hyperbilirubinaemia † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Infections and infestations
Nasopharyngitis † 1	1/3 (33.33%)	1/7 (14.29%)	2/40 (5.00%)	3/47 (6.38%)
Influenza † 1	1/3 (33.33%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Cytomegalovirus infection † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Upper respiratory tract infection † 1	1/3 (33.33%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Urinary Tract Infection † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Bacterial Infection † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Infected epidermal cyst † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Infection † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Pneumocystis jiroveci pneumonia † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Injury, poisoning and procedural complications
Contusion † 1	1/3 (33.33%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Excoriation † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Fall † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Procedural Pain † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Investigations
Haemoglobin decreased † 1	2/3 (66.67%)	2/7 (28.57%)	9/40 (22.50%)	11/47 (23.40%)
Alanine aminotransferase increased † 1	1/3 (33.33%)	2/7 (28.57%)	7/40 (17.50%)	9/47 (19.15%)
Weight decreased † 1	2/3 (66.67%)	2/7 (28.57%)	6/40 (15.00%)	8/47 (17.02%)
Aspartate aminotransferase increased † 1	0/3 (0.00%)	1/7 (14.29%)	8/40 (20.00%)	9/47 (19.15%)
Blood alkaline phosphatase increased † 1	1/3 (33.33%)	0/7 (0.00%)	3/40 (7.50%)	3/47 (6.38%)
Blood lactate dehydrogenase increased † 1	0/3 (0.00%)	0/7 (0.00%)	4/40 (10.00%)	4/47 (8.51%)
Electrocardiogram QT prolonged † 1	0/3 (0.00%)	2/7 (28.57%)	1/40 (2.50%)	3/47 (6.38%)
Blood phosphorus increased † 1	2/3 (66.67%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Blood urea increased † 1	1/3 (33.33%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Blood bilirubin increased † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Electrocardiogram ST-T change † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Electrocardiogram ST-T segment elevation † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Electrocardiogram T wave inversion † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Renal Function Test abnormal † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Gamma-glutamyltransferase increased † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Metabolism and nutrition disorders
Decreased appetite † 1	3/3 (100.00%)	4/7 (57.14%)	21/40 (52.50%)	25/47 (53.19%)
Hypokalaemia † 1	1/3 (33.33%)	2/7 (28.57%)	7/40 (17.50%)	9/47 (19.15%)
Hypophosphataemia † 1	0/3 (0.00%)	1/7 (14.29%)	9/40 (22.50%)	10/47 (21.28%)
Hyponatraemia † 1	0/3 (0.00%)	2/7 (28.57%)	6/40 (15.00%)	8/47 (17.02%)
Hypermagnesaemia † 1	1/3 (33.33%)	1/7 (14.29%)	4/40 (10.00%)	5/47 (10.64%)
Hypoalbuminaemia † 1	0/3 (0.00%)	1/7 (14.29%)	5/40 (12.50%)	6/47 (12.77%)
Hypocalcaemia † 1	1/3 (33.33%)	1/7 (14.29%)	4/40 (10.00%)	5/47 (10.64%)
Hyperkalaemia † 1	0/3 (0.00%)	1/7 (14.29%)	4/40 (10.00%)	5/47 (10.64%)
Hypomagnesaemia † 1	0/3 (0.00%)	0/7 (0.00%)	4/40 (10.00%)	4/47 (8.51%)
Dehydration † 1	0/3 (0.00%)	0/7 (0.00%)	3/40 (7.50%)	3/47 (6.38%)
Hyperuricaemia † 1	1/3 (33.33%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Tumour lysis syndrome † 1	0/3 (0.00%)	0/7 (0.00%)	3/40 (7.50%)	3/47 (6.38%)
Hypercalcaemia † 1	0/3 (0.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/3 (33.33%)	1/7 (14.29%)	3/40 (7.50%)	4/47 (8.51%)
Back Pain † 1	1/3 (33.33%)	2/7 (28.57%)	2/40 (5.00%)	4/47 (8.51%)
Musculoskeletal stiffness † 1	1/3 (33.33%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Osteoarthritis † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Pain in extremity † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Periarthritis † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Muscle Spasms † 1	0/3 (0.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Musculoskeletal pain † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain † 1	1/3 (33.33%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Tumour associated fever † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Nervous system disorders
Dysgeusia † 1	3/3 (100.00%)	4/7 (57.14%)	24/40 (60.00%)	28/47 (59.57%)
Headache † 1	1/3 (33.33%)	0/7 (0.00%)	6/40 (15.00%)	6/47 (12.77%)
Peripheral Sensory neuropathy † 1	3/3 (100.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Akathisia † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Carotid arteriosclerosis † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Somnolence † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Psychiatric disorders
Insomnia † 1	2/3 (66.67%)	0/7 (0.00%)	3/40 (7.50%)	3/47 (6.38%)
Renal and urinary disorders
Proteinuria † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Pollakiuria † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Respiratory, thoracic and mediastinal disorders
Hypoxia † 1	1/3 (33.33%)	3/7 (42.86%)	2/40 (5.00%)	5/47 (10.64%)
Upper respiratory tract inflammation † 1	0/3 (0.00%)	0/7 (0.00%)	4/40 (10.00%)	4/47 (8.51%)
Cough † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Oropharyngeal pain † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Pleural effusion † 1	0/3 (0.00%)	1/7 (14.29%)	1/40 (2.50%)	2/47 (4.26%)
Hiccups † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Pneumonitis † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Skin and subcutaneous tissue disorders
Rash † 1	0/3 (0.00%)	1/7 (14.29%)	4/40 (10.00%)	5/47 (10.64%)
Dry Skin † 1	0/3 (0.00%)	0/7 (0.00%)	2/40 (5.00%)	2/47 (4.26%)
Hyperhidrosis † 1	1/3 (33.33%)	0/7 (0.00%)	1/40 (2.50%)	1/47 (2.13%)
Erythema † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Haemorrhage subcutaneous † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Henoch-Schonlein purpura † 1	0/3 (0.00%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
Rash macular † 1	1/3 (33.33%)	0/7 (0.00%)	0/40 (0.00%)	0/47 (0.00%)
Vascular disorders
Phlebitis † 1	1/3 (33.33%)	2/7 (28.57%)	1/40 (2.50%)	3/47 (6.38%)
Hypotension † 1	2/3 (66.67%)	1/7 (14.29%)	0/40 (0.00%)	1/47 (2.13%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (14.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation
• Phone: 888-260-1599
• EMail: ClinicalTrialDisclosure@celgene.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT01456039
• Other Study ID Numbers: ROMI-TCL-001
• First Submitted: October 18, 2011
• First Posted: October 20, 2011
• Results First Submitted: July 11, 2016
• Results First Posted: August 19, 2016
• Last Update Posted: February 11, 2019