Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Romidepsin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Histone Deacetylase Inhibitors

Enzyme Inhibitors

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.

Intravenous dosing for 4 hours on Days 1, 8, and 15 of each 28-day cycle

Toru Sasaki

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

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

A Japanese Phase 1/2, Multicenter, Open-label Study to Assess the Efficacy, Tolerability, Safety and Pharmacokinetics of Romidepsin in Subjects With the Progressive or Relapsed Peripheral T-cell Lymphoma

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

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

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.

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.

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.

The maximum observed plasma concentration of romidepsin (Cmax) obtained directly from the observed concentration versus time data

The time to first maximum observed plasma concentration of romidepsin after a single dose on Day 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.

The apparent total clearance of romidepsin after a single dose on Day 1, calculated as dose/AUC0-infinity.

Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz

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

Maximum observed concentration in plasma at steady state

Observed time to first maximum plasma concentration at steady state

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.

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)

Cmax of Romidepsin: accumulation ratio based on Cmax calculated as Cmax,ss/Cmax

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

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.

TTR for PTCL was defined as the time in days from first dose date to the first date of objective disease response.

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 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

Celgene

Romidepsin 9mg/m\^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle

Phase 1: Romidepsin 9mg/m^2

Romidepsin 14mg/m\^2 by intravenous (IV) infusion on Days 1, 8, 15 of each 28-day cycle.

Phase 1: Romidepsin 14mg/m^2

Phase 2: Romidepsin 14mg/m^2

Total: Romidepsin 14mg/m^2

Total

Age, Continuous

<65 years

≥65 years

Age, Customized

Sex: Female, Male

PTCL

CTCL

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.

Disease Type by Investigator

0 = (Fully Active)

1 = (Restrictive but ambulatory)

2 = (Ambulatory but unable to work)

3 = (Limited self care)

4 = (Completely Disabled)

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)

Eastern Cooperative Oncology Group (ECOG)

BSA is the total surface area of the body and was used to calculate the dosage for romidepsin.

Body Surface Area (BSA)

Intent to Treat (ITT) includes all participants who received at least one dose of romidepsin.

Anne McClain, Senior Manager, Clinical Trial Disclosure

Phase 1: Cohort 1: Romidepsin 9mg/m^2

Phase 1: Cohort 2: Romidepsin 14mg/m^2

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.

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)

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

Percentage of PTCL Participants With an Overall Best Response in Accordance With a Modified International Workshop Response Criteria (IWC) 1999 in Phase 2

Any 1 TEAE

TEAE related to any study drug

TEAE with CTCAE Grade 3 or greater

TEAE with CTCAE ≥Grade 3 related to study drug

≥ 1 serious TEAE

Serious TEAE related to study drug

TEAE leading to discontinuation of study drug

TEAE related leading to discontinuation of drug

TEAE leading to dose held of study drug

Related TEAE leading to dose held of study drug

TEAE leading to dose reduction of study drug

Related TEAE leading to dose reduction of drug

TEAE leading to dose interruption of study drug

Related TEAE leading to dose interruption of drug

At least one TEAE with NCI CTCAE Grade 5

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

Participants With Treatment-Emergent Adverse Events (TEAEs) Associated With Romidepsin

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.

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

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.

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

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.

Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 1

Time to Maximum Plasma Concentration of Romidepsin (Tmax) in Phase 1

Terminal Phase Half-life of Romidepsin (t½) in Phase 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.

Apparent Total Clearance of Romidepsin (CL/F) of Romidepsin in Phase 1

Apparent Volume of Distribution (Vz/F) of Romidepsin in Phase 1

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

Cmax, ss of Romidepsin in Phase 1 at Cycle 1, Day 15

Tmax,ss of Romidepsin in Phase 1 at Cycle 1, Day 15

Terminal Phase Half-life of Romidepsin (t½) in Phase 1 at Cycle 1, Day 15

AUC0-t, Accumulation Ratio of Romidepsin in Phase 1, Cycle 1

Cmax Accumulation Ratio of Romidepsin in Phase 1, Cycle 1

QTcB >450 msec

QTcB >480 msec

QTcB >500 msec

QTcB increase from predose >30 msec

QTcB increase from predose >60 msec

QTcF >450 msec

QTcF >480 msec

QTcF >500 msec

QTcF increase from predose >30 msec

QTcF increase from predose >60 msec

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

The Percentage of Participants With Abnormal Q-wave and T Wave Intervals

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

Percentage of PTCL Participants With the Best Response in Accordance With the Modified 2007 International Workshop Response Criteria as Assessed by IER

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)

Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 1999 IWC as Assessed by IER

Time to Response (TTR) for PTCL Participants With at Least a PR Based on the Modified 2007 IWC as Assessed by IER

Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 1999 IWC as Assessed by the IER.

Kaplan Meier Estimate of Duration of Response (DOR) for PTCL Responders Based on the Modified 2007 IWC as Assessed by the IER.

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

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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