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NCT01456039 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2019-02-11

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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)

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 1

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outcome · POSTED

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

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outcome · POSTED

Terminal Phase Half-life of Romidepsin (t½) in Phase 1

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Cmax Accumulation Ratio of Romidepsin in Phase 1, Cycle 1

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Kaplan Meier Estimate of Time to Progression (TTP) in PTCL Participants Based on the 1999 IWC as Assessed by IER

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outcome · POSTED

Kaplan Meier (K-M) Estimate of Time to Progression (TTP) in PTCL Participants Based on the Modified 2007 IWC as Assessed by IER

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
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); * Age ≥20 years; * Written informed consent; * Progressive Disease following at least one systemic therapy or refractory to at least one prior systemic therapy; * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; * Sufficient functions of bone marrow or other organs as evidenced by * 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 * Serum potassium ≥ lower limit of normal (LLN) and magnesium * Patients for whom at least 1 measurable lesion is confirmed in the lesion assessment before enrollment; and * Negative urine or serum pregnancy test on females of childbearing potential. Exclusion Criteria: Confirmation should be made before enrollment, and the subjects corresponding to the criteria should not be enrolled. 1. Subjects in whom central nervous lymphoma is recognized during the screening period (If brain metastasis is suspected clinically, CT should be performed.) 2. 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) 3. 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) 4. 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) 5. Subjects undergoing radiation therapy, PUVA therapy or TSEB for the purpose of treatment of the target disease within 22 days before C1D1 (including C1D1) 6. Subjects using other investigational products within 22 days before C1D1 (including C1D1) (using antibody drugs only within 3 months before C1D1) 7. Subjects undergoing blood transfusion and using G-CSF within 8 days before C1D1 (including C1D1) 8. Subjects with the following abnormalities in the cardiac function 1. Congenital QT prolongation syndrome 2. QTc interval \>480 msec 3. Myocardial infarction within 6 months before C1D1. Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may occur 4. Significant ECG abnormalities including atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) 5. Symptomatic coronary artery disease (CAD) (e.g., Angina Canadian Class II-IV). 6. An ECG recorded at screening showing significant ST depression (ST depression of ≥2 mm, measured from isoelectric line to the ST segment at a point 60 msec at the end of the QRS complex). If there is any doubt, the subject should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present. 7. Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions and/or ejection fraction \<40% by MUGA scan or \<50% by echocardiogram and/or MRI 8. A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD) 9. Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or other causes (if there is any doubt, see ejection fraction criteria above) 10. Uncontrolled hypertension, i.e., systolic blood pressure (BP) is greater than or equal to 160 mmHg or diastolic BP is greater than or equal to 95 mmHg; subjects who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) 11. Subjects with cardiac arrhythmia requiring an anti-arrhythmic drug 9. Concomitant use of a drug which may induce significant QT prolongation (refer to 9.2. Prohibited Concomitant Medications and Procedures.) 10. Concomitant use of strong or moderate CYP3A4 inhibitors which include grapefruit juice 11. Concomitant use of CYP3A4 inducers which include St John's Wort (1st step only) 12. 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. 13. Clinically important active infections 14. 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. 15. 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. 16. 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. 17. Subjects who are during recovery process from severe wound or fracture. 18. Subjects with a history of allogeneic stem cell transplantation 19. Patients who are breast-feed during period of the IP administration or within 28 days after the end of the IP administration. 20. 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) 21. Subject with a history of hematological malignant tumor (other than T-cell lymphoma) 22. Subjects for whom transfusion of red blood cells or platelets is impossible (such as clinical state and religious beliefs) 23. Significant medical or psychiatric situation by which all of the study procedures may not be observed 24. Subjects receiving romidepsin in the past (Other HDAC inhibitors are acceptable) 25. Subjects judged to be inappropriate for this study by the investigator or sub-investigator. 26. Concomitant use of rifampicin.
healthy Volunteers
false
minimum Age
20 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Drug: Romidepsin
    label
    Romidepsin
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Romidepsin
    description
    Intravenous dosing for 4 hours on Days 1, 8, and 15 of each 28-day cycle
    name
    Romidepsin
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
51
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. 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
    measure
    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)
    time Frame
    Up to Day 28; Cycle 1
  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
    measure
    Percentage of PTCL Participants With an Overall Best Response in Accordance With a Modified International Workshop Response Criteria (IWC) 1999 in Phase 2
    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
secondary Outcomes
  1. 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.
    measure
    Participants With Treatment-Emergent Adverse Events (TEAEs) Associated With Romidepsin
    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
  2. 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.
    measure
    Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t) of Romidepsin in Phase 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
  3. 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.
    measure
    Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Romidepsin in Phase 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
  4. description
    The maximum observed plasma concentration of romidepsin (Cmax) obtained directly from the observed concentration versus time data
    measure
    Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 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
  5. description
    The time to first maximum observed plasma concentration of romidepsin after a single dose on Day 1.
    measure
    Time to Maximum Plasma Concentration of Romidepsin (Tmax) in Phase 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
  6. 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.
    measure
    Terminal Phase Half-life of Romidepsin (t½) in Phase 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.
  7. description
    The apparent total clearance of romidepsin after a single dose on Day 1, calculated as dose/AUC0-infinity.
    measure
    Apparent Total Clearance of Romidepsin (CL/F) of Romidepsin in Phase 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.
  8. description
    Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz
    measure
    Apparent Volume of Distribution (Vz/F) of Romidepsin in Phase 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
  9. 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
    measure
    AUC0-t, at Steady State (ss) of Romidepsin in Phase 1 at Cycle 1, Day 15
    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
  10. description
    Maximum observed concentration in plasma at steady state
    measure
    Cmax, ss of Romidepsin in Phase 1 at Cycle 1, Day 15
    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
  11. description
    Observed time to first maximum plasma concentration at steady state
    measure
    Tmax,ss of Romidepsin in Phase 1 at Cycle 1, Day 15
    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
  12. 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.
    measure
    Terminal Phase Half-life of Romidepsin (t½) in Phase 1 at Cycle 1, Day 15
    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.
Full study description
brief Summary
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
detailed Description
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
Source references
references
  1. citation
    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.
    pmid
    28664499
    type
    DERIVED
Source notices and limitations
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    Preserved source evidence · Not medical advice