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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00426764
Other study ID # GPI-06-0002
Secondary ID 2006-006228-21
Status Completed
Phase Phase 2
First received
Last updated
Start date June 19, 2007
Est. completion date May 17, 2018

Study information

Verified date January 2020
Source Celgene
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the activity of romidepsin in patients with progressive or relapsed peripheral T-cell lymphoma (PTCL) who have already been treated with systemic therapy.


Description:

This is a Phase II, non-randomized, open-label, single-arm trial. This study is designed on the basis of complete response (CR) or unconfirmed CR [CR(u)] as the measure of efficacy, based on the best overall response of each patient. The sample size of 65 patients evaluable for efficacy would yield lower 95% confidence limits on the rate of CR + CR(u) that would range from 2.2% to 7.7%, if the observed rate of CR + CR(u) ranges from 8% to 15%. The study was amended to include an Extension Phase, during which patients at non-US sites who are benefitting from treatment can continue to receive romidepsin. The Extension Study Phase is active in EU countries where currently no Marketing Authorisation exists for romidepsin. Patients may remain on study until progressive disease occurs or they withdraw their consent and only serious adverse events and study drug administration data will continue to be collected and reported for these patients.


Other known NCT identifiers
  • NCT00924378

Recruitment information / eligibility

Status Completed
Enrollment 131
Est. completion date May 17, 2018
Est. primary completion date November 11, 2010
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

Patients must fulfill all of the following criteria to be eligible for study participation and have:

- Histologically confirmed PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, extranodal natural killer (NK)/T-cell lymphoma nasal type, enteropathy- type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous ?d T-cell lymphoma (excludes mycosis fungoides or Sezary syndrome), transformed mycosis fungoides, hepatosplenic T-cell lymphoma, anaplastic large cell lymphoma (ALCL; anaplastic lymphoma kinase [ALK]-1 negative), or patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after autologous stem cell transplant (ASCT);

- Age =18 years;

- Written informed consent;

- Progressive disease following at least one systemic therapy or refractory to at least one prior systemic therapy;

- Measurable disease according to the International Workshop Response (IWC) criteria and/or measurable cutaneous disease;

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;

- Serum potassium =3.8 mmol/L and magnesium =0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria);

- Negative urine or serum pregnancy test on females of childbearing potential; and

- All women of childbearing potential must use an effective barrier method of contraception (either an intrauterine contraceptive device [IUCD] or double barrier method using condoms or a diaphragm plus spermicide) during the treatment period and for at least 1 month thereafter. Male patients should use a barrier method of contraception during the treatment period and for at least 1 month thereafter. Hormonal methods of contraception such as the contraceptive pill or patch (particularly those containing ethinyl-estradiol) should be avoided due to a potential drug interaction.

Exclusion Criteria:

Patients are ineligible for entry if any of the following criteria are met:

- Known central nervous system (CNS) lymphoma [computed tomography (CT) or magnetic resonance imaging (MRI) scans are required only if brain metastasis is suspected clinically];

- Chemotherapy or immunotherapy within 4 weeks of study entry (6 weeks if nitrosoureas given);

- Initiation of corticosteroids during study (defined as 7 days prior to Cycle 1 Day 1[C1D1] until study drug discontinuation)

- Patients treated with a pulse of steroids were to discontinue steroid use 7 days prior to C1D1 and have a repeat CT scan and disease assessment after discontinuation of corticosteroids and before starting romidepsin;

- Concomitant use of any other anti-cancer therapy;

- Concomitant use of any investigational agent;

- Use of any investigational agent within 4 weeks of study entry;

- Any known cardiac abnormalities such as:

- Congenital long QT syndrome;

- QTc interval >480 milliseconds (msec);

- A myocardial infarction within 6 months of C1D1. Patients with a history of myocardial infraction 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 participate;

- Other significant electrocardiogram (ECG) abnormalities including 2nd degree 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. In any patient in whom there is doubt, the patient should be referred to a cardiologist for evaluation;

- 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 in any doubt, the patient 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;

- 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);

- Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above);

- Uncontrolled hypertension, i.e., blood pressure (BP) of =160/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria;

- Any cardiac arrhythmia requiring anti-arrhythmic medication;

- Serum potassium <3.8 mmol/L or serum magnesium <0.85 mmol/L (electrolyte abnormalities can be corrected with supplementation to meet inclusion criteria);

- Concomitant use of drugs that may cause a significant prolongation of the QTc;

- Concomitant use of CYP3A4 significant or moderate inhibitors;

- Concomitant use of therapeutic warfarin or another anticoagulant due to a potential drug interaction. Use of a small dose of a anticoagulant to maintain patency of venous access port and cannulas is permitted;

- Clinically significant active infection;

- Known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C;

- Previous extensive radiotherapy involving =30% of bone marrow (e.g., whole pelvis, half spine), excluding patients who have had total body irradiation as part of a conditioning regimen for ASCT;

- Major surgery within 2 weeks of study entry;

- Previous allogeneic stem cell transplant;

- Inadequate bone marrow or other organ function as evidenced by:

- Hemoglobin <9 g/dL (transfusions and/or erythropoietin are permitted);

- Absolute neutrophil count (ANC) =1.0 × 10^9 cells/L [patients with neutropenia (ANC 1-1.5 10^9 cells/L) as a function of their disease may be supported with granulocyte-colony stimulating factor (G-CSF)];

- Platelet count <100 × 10^9 cells/L or platelet count <75 × 10^9 cells/L if bone marrow disease involvement is documented;

- Total bilirubin >2.0 × upper limit of normal (ULN) or >3.0 × ULN in the presence of demonstrable liver metastases;

- Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) >2.0 × ULN or >3.0 × ULN in the presence of demonstrable liver metastases; or

- Serum creatinine >2.0 × ULN;

- Patients who are pregnant or breast-feeding;

- Coexistent second malignancy or history of prior solid organ malignancy within previous 3 years (excluding basal or squamous cell carcinoma of the skin, and in situ carcinoma of the cervix (CIN 1) that has been treated curatively);

- Any prior history of a hematologic malignancy (other than T-cell lymphoma);

- Any significant medical or psychiatric condition that might prevent the patient from complying with all study procedures; or

- Prior exposure to romidepsin (other histone deacetylase inhibitors are allowed).

Study Design


Intervention

Drug:
Romidepsin
Romidepsin intravenously (through a vein) over 4 hours on Days 1, 8 and 15 of each 28-day cycle.

Locations

Country Name City State
Australia Peter MacCallum Cancer Centre East Melbourne
Australia St. Vincent Hospital Fitzroy
Australia Mater Private Medical Centre - Haematology and Oncology Clinics of Australasia Research Centre South Brisbane Queensland
Australia Royal North Shore Hospital St Leonards
Czechia University Hospital Brno Brno
Czechia University Hospital Hradec Kralove Hradec Kralove
Czechia University Hospital of Kralovske Vinohrady Prague 10
Czechia Charles University General Hospital Prague 2
France Polyclinique Bordeaux Nord Aquitaine Bordeaux
France Hopital Henri Mondor Créteil
France Hopital Claude Huriez Lille
France CHU Nantes Hotel Dieu Nantes
France Hopital Saint-Louis Paris
France Service des Maladies du Sang Pessac
France Centre Hospitalier Lyon Sud Pierre Bénite
France Centre Eugene Marquis Rennes
France Centre Henri Becquerel Rouen Cedex
Germany Charite Universitatsmedizin Berlin campus Virchow Klinikum Centrum fur Tumormedizin Berlin
Germany Krankenhaus Nordwest Frankfurt a.M.
Germany Georg-August-Universität Göttingen Göttingen
Germany Uniklinik Koln Köln
Germany Klinikum der Universitat Munchen-Grosshadern Muenchen
Germany Klinikum Nurnberg Nord Nürnberg
Germany UKT Universitaetsklinikum Tuebingen Tuebingen
Poland Klinika Hematologii Akademickie Centrum Kliniczne Akademii Medycznej w Gdansku Gdansk
Poland Oddzial Kliniczny Kliniki Hematologii Kraków
Poland Wojewodzki Szpital Specjalistczny im. Mikolaja Kopernika Lodz
Poland Klinika Nowotworow Ukladu Chlonnego Warszawa
Spain Hospital Universitario Vall D Hebron Barcelona
Spain Hospital de La Princesa Madrid
Spain Hospital Universitario La Paz Madrid
Spain Clinica Universitaria de Navarra Pamplona
Spain Hospital Universitario de Salamanca Salamanca
Spain Hospital Marques de Valdecilla Santandar
Sweden Lund University Hosptial Lund
Sweden Akademiska Sjukhuset Uppsala
Ukraine Dnipropetrovsk State Medical Academy Dnipropetrovsk
Ukraine National Cancer Institute Department Of Conservative Methods Of Treatment Kyiv
Ukraine R.E.Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology Kyiv
Ukraine Institute of Blood Pathology and Transfusion Medicine of the AMS of Ukraine Lviv
United Kingdom Barts Cancer Institute, Queen Mary University of London, Charterhouse Square London
United Kingdom Catherine Lewis Centre - Hematology Department London
United Kingdom Guy's and St. Thomas' Hospital London
United Kingdom Royal Free Hospital London Hampstead
United Kingdom Somers Cancer Research Building Southampton
United States Cancer Care and Hematology Specialists of Chicagoland Arlington Heights Illinois
United States Winship Cancer Institute of Emory University Atlanta Georgia
United States Augusta Oncology Associates, P.C. Augusta Georgia
United States Rocky Mountain Cancer Centers-Aurora Aurora Colorado
United States St. Agnes - Medical Center Baltimore Maryland
United States Mamie McFadden Ward Center Beaumont Texas
United States Center for Cancer And Blood Disorders Bethesda Maryland
United States Center for Cancer Research CAMC Bethesda Maryland
United States Tufts Medical Center Boston Massachusetts
United States Minnesota Oncology Hematology, PA Burnsville Minnesota
United States Hematology Oncology Assoc. of IL Orchard Research LLC Chicago Illinois
United States Rush University Medical Center Chicago Illinois
United States Taussig Cancer Center Cleveland Clinic Foundation Cleveland Ohio
United States Methodist Charlton Cancer Center Dallas Texas
United States UT Southwestern Medical Center Simmons Comprehensive Cancer Center Dallas Texas
United States Henry Ford Hospital Detroit Michigan
United States El Paso Cancer Treatment Center El Paso Texas
United States Texas Oncology, P.A.-Fort Worth Fort Worth Texas
United States Hackensack University Medical Center Hackensack New Jersey
United States UT MD Anderson Cancer Center Houston Texas
United States Moore UCSD Cancer Center La Jolla California
United States UCLA Division of Hematology Oncology Los Angeles California
United States Consultants in Blood Disorders and Cancer Louisville Kentucky
United States Central Georgia Cancer Care Macon Georgia
United States Accelerated Community Oncology Research Network Inc ACORN Memphis Tennessee
United States Allison Cancer Center Midland Texas
United States Yale University New Haven Connecticut
United States Columbia University Medical Center New York New York
United States Memorial Sloan-Kettering Cancer Center New York New York
United States Weill Cornell Medical College New York New York
United States Nebraska Cancer Specialists Omaha Nebraska
United States Cancer Centers of Florida, PA Orlando Florida
United States US Oncology Plano Texas
United States Northwest Cancer Specialists, P.C. Portland Oregon
United States St. Joseph Oncology, Inc Saint Joseph Missouri
United States Arch Medical Services Saint Louis Missouri
United States HOAST San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States University of California, San Francisco San Francisco California
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States H. Lee Moffitt Cancer Center and Research Institute Tampa Florida
United States Tyler Cancer Center Tyler Texas
United States Texas Oncology, PA Waco Texas
United States Georgetown University IRB Washington District of Columbia
United States Washington Hospital Center Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Australia,  Czechia,  France,  Germany,  Poland,  Spain,  Sweden,  Ukraine,  United Kingdom, 

References & Publications (4)

Coiffier B, Pro B, Prince HM, Foss F, Sokol L, Greenwood M, Caballero D, Borchmann P, Morschhauser F, Wilhelm M, Pinter-Brown L, Padmanabhan S, Shustov A, Nichols J, Carroll S, Balser J, Balser B, Horwitz S. Results from a pivotal, open-label, phase II st — View Citation

Foss F, Pro B, Miles Prince H, Sokol L, Caballero D, Horwitz S, Coiffier B. Responses to romidepsin by line of therapy in patients with relapsed or refractory peripheral T-cell lymphoma. Cancer Med. 2017 Jan;6(1):36-44. doi: 10.1002/cam4.939. Epub 2016 Dec 16. — View Citation

Horwitz S, Coiffier B, Foss F, Prince HM, Sokol L, Greenwood M, Caballero D, Morschhauser F, Pinter-Brown L, Iyer SP, Shustov A, Nichols J, Balser J, Balser B, Pro B. Utility of ¹8fluoro-deoxyglucose positron emission tomography for prognosis and response — View Citation

Shustov A, Coiffier B, Horwitz S, Sokol L, Pro B, Wolfson J, Balser B, Eisch R, Popplewell L, Prince HM, Allen SL, Piekarz R, Bates S. Romidepsin is effective and well tolerated in older patients with peripheral T-cell lymphoma: analysis of two phase II trials. Leuk Lymphoma. 2017 Oct;58(10):2335-2341. doi: 10.1080/10428194.2017.1295143. Epub 2017 Mar 7. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With a Complete Response According to the International Workshop Response Criteria (IWC) for Non-Hodgkin's Lymphomas (NHL) Assessed by an Independent Review Committee Complete Response (CR): >75% decrease in size aggregate of nodal index lesions (large and small), complete disappearance of extranodal and non-index lesions; total disappearance of clinical disease including skin involvement; disease-related signs and symptoms, normalization of biochemical abnormalities and reduction in size of spleen or liver so no longer palpable. Unconfirmed CR: all above criteria except all nodal index lesions must have regressed >75% in the sum of the product diameters (SPD) from baseline. Individual nodes previously confluent must have regressed by >75% in their SPD. Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary Percentage of Participants With Objective Disease Response Objective disease response was defined as patients with a Complete Response, Unconfirmed Complete Response or a Partial Response (PR) according to the IWC 1999 assessed by an independent review committee: CR, Cru defined above, PR defined as =50% decrease in size of 6 largest dominant nodes and/or nodal masses & extranodal index lesions and no increase of non-index lesions, liver, or spleen; no new sites of disease evident; skin lesions decreased by =50%. Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary Duration of Objective Disease Response Duration of response 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 and was determined using Kaplan-Meier product-limit estimates. Progression was defined as: a =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. Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary Duration of Complete Disease Response Duration of response was defined as the number of days from the date of the first disease response (Complete or Unconfirmed Complete) until the date of progression and was determined using Kaplan-Meier product-limit estimates. Progression was defined as: a =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. Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary Time to Disease Progression 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 as reported by the independent review committee and was determined using Kaplan-Meier product-limit estimates. Response was assessed after every 2 cycles of treatment and at completion of therapy, up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary Change in Eastern Cooperative Oncology Group (ECOG) Performance Status The ECOG scale is as follows: Grade 0: Fully active, able to perform all pre-disease activities without restriction; Grade 1: Restricted in physically strenuous activity, ambulatory, able to carry out light work; Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or chair. Data reported is the shift from Baseline ECOG score to best on-study assessment score. From Baseline up until 30 September 2012 (data cutoff for analysis). Maximum duration on study was 1931 days.
Secondary Number of Participants With Treatment Emergent Adverse Events (TEAEs) An adverse event or experience (AE) is defined as any untoward medical occurrence, which does not necessarily have to have a causal relationship with this treatment. A serious AE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is an important medical event or condition. Related AEs are defined as those considered by the Investigator to have a possible, probable, or very likely/certain relationship to the study drug. AEs were graded as mild (1), moderate (2), severe (3), lifethreatening (4), or death (5). TEAEs occurred from the first dose of study medication through the end of the study (30 days post last dose) or any event that was present at baseline but worsened in intensity or was subsequently considered drug-related by the Investigator through end of study. From first dose of study treatment until the final study visit, which occurred 30 days after receiving the last dose. Mean duration of treatment up until 30 September 2012 (data cutoff for analysis) was 169 days.
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