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

NCT01456039 | Completed Phase 1 Results

• 1 other identifier: ROMI-TCL-001
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 17

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

Conditions

Lymphoma, T-cell, Peripheral

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-limiting Toxicity (DLT) in Accordance With National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 as Determined by the Efficacy and Safety Evaluation Committee (ESEC)

  DLT was defined as an adverse event (AE) occurring in Cycle 1 in Phase 1 and judged that the causal relationship to the investigational product could not be denied. The severity of all AEs was graded based upon the NCI CTCAE version 3.0. DLTs were defined as: • Grade 4 Hemoglobin \<6.5 g/dL • Grade 4 Neutrophil \<500/μL continuing for at least 5 days • Febrile neutropenia (Grade 4 neutropenia caused by fever and ≥ 38.5° C for more than 1 hour) • Grade 4 thrombocyte (\< 25,000/μL), or thrombocytopenia with hemorrhage requiring platelet transfusion • Nausea, vomiting, or diarrhea at \> grade 3 in spite of treatment • Grade 3 ALT (alanine aminotransferase) or AST (aspartate aminotransferase) values continued for 7 days. • Grade 4 ALT or AST • Grade 2 arrhythmia • Grade 4 non-hematological AEs • Other grade 3 non-hematological AEs except transient fatigue, anorexia, hyponatremia, and tumor lysis syndrome • Other AEs leading to discontinuation of administration

  Up to Day 28; Cycle 1

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

  Objective disease response in PTCL was defined as patients with a complete response (CR), unconfirmed complete response (CRu) or a partial response (PR) according to modified IWC 1999 criteria and assessed by an independent efficacy reviewer. A CR is \>75% decrease in size of maximum 6 largest target within nodal and extranodal lesions, complete disappearance of other nodal and extranodal; total disappearance of clinical disease; disease-related signs and symptoms, normalization of biochemical abnormalities, disappearance of spleen, liver, or kidney enlargement; no bone marrow (BM) involvement, no new sites of disease. CRu: all above criteria fulfilled except for BM involvement is indeterminate. PR: a ≥50% decrease in size of 6 largest target lesions and no increase other nodal and extranodal; no progression of clinical disease; disease-related signs and symptoms, normalization or biochemical abnormalities, no progression in size of liver, spleen, or kidney; and no new sites of disease

  Tumor assessments performed every 2 months; median follow-up time was 100 days; up to the data cut-off of 28 July 2015

Secondary Outcomes (22)

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

  Day 1 of study drug through 30 days after the last dose of study drug or discontinuation date; Up to data cut-off of 28 July 2015; maximum follow up time was 184.3 weeks

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

  Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration

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

  Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration

• Maximum Plasma Concentration (Cmax) of Romidepsin in Phase 1

  Day 1 at Cycle 1; collected at 0 (pre-dose), 1, 2, 3, and 4 (at the end of administration) hours after the start of administration, 0.25 (15 minutes), 0.5 (30 minutes), 1, 2, 4, 6, 20, and 44 hours after the end of administration

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

  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

Study Arms (1)

Romidepsin

EXPERIMENTAL

Patients will receive romidepsin intravenously for 4 hours on Days 1, 8, and 15 of each 28-day cycle until when/if a discontinuation criterion, e.g., disease progression, severe adverse events, or consent withdrawal.

Drug: Romidepsin

Interventions

Romidepsin DRUG

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

Romidepsin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Subjects in whom central nervous lymphoma is recognized during the screening period (If brain metastasis is suspected clinically, CT should be performed.)
• Subjects undergoing chemotherapy or immunotherapy for the purpose of treatment of the target disease within 22 days before C1D1 (including C1D1) (using antibody drugs only within 3 months before C1D1)
• Subjects receiving local application of steroids within 15 days before C1D1 (including C1D1) Use of steroids for the purpose other than that of treatment of the target disease should be allowed (Only CTCL subjects)
• Subjects receiving systemic application of steroids within 22 days before C1D1 (including C1D1) (It is acceptable to continue the use of the steroid for the purpose of treatment of the target disease,which administered in doses ≤ 10mg/day prednisolone or equivalent dose of other glucocorticoid. However increase of steroid dose cannot be allowed during the study period)
• Subjects undergoing radiation therapy, PUVA therapy or TSEB for the purpose of treatment of the target disease within 22 days before C1D1 (including C1D1)
• Subjects using other investigational products within 22 days before C1D1 (including C1D1) (using antibody drugs only within 3 months before C1D1)
• Subjects undergoing blood transfusion and using G-CSF within 8 days before C1D1 (including C1D1)
• Subjects with the following abnormalities in the cardiac function
• Congenital QT prolongation syndrome
• QTc interval \>480 msec
• 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
• Significant ECG abnormalities including atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• Symptomatic coronary artery disease (CAD) (e.g., Angina Canadian Class II-IV).
• 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.
• 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

Sponsors & Collaborators

• Celgene: lead

Study Sites (17)

Nagoya Daini Red Cross Hospital

Nagoya, Aichi-ken, 466-8650, Japan

Location

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577:, Japan

Location

Ehime University Hospital

Tōon, Ehime, 791-0295, Japan

Location

Chugoku Central Hospital

Fukuyamashi, Hiroshima, 720-0001, Japan

Location

Sapporo Hokuyu Hospital

Sapporo, Hokkaido, 003-0006, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Tokai University School of Medicine

Isehara, Kanagawa, 259-1193, Japan

Location

Kochi Medical School Hospital

Nankoku, Kochi, 783-8505, Japan

Location

Kinki University Hospital

Sayama, Osaka, 589-8511, Japan

Location

National Cancer Center Hospital

Chūō, Tokyo, 104-0045, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, Tokyo, 150-8935, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

University hospital, Kyoto prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Tohoku University Hospital

Miyagi, 980-8574, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

romidepsin

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@celgene.com

888-260-1599

Study Officials

• Toru Sasaki

  Celgene K.K.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: October 20, 2011
• Study Start: December 1, 2011
• Primary Completion: July 28, 2015
• Study Completion: December 14, 2018
• Last Updated: February 11, 2019
• Results First Posted: August 19, 2016

Record last verified: 2019-01

Locations

JP (17)