Progressive or relapsed Peripheral T-Cell Lymphoma (PTCL) MedDRA version: 8.1 Level: LLT Classification code 10034624 Term: Peripheral T-cell lymphoma unspecified NOS
Conditions
Interventions
Product Name: Romidepsin
Product Code: FK228
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Romidepsin
CAS Number: 128517-07-7
Current Sponsor code: FK228 / FR901228 / NSC6
Sponsors
Gloucester Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed PTCL NOS, angioimmunoblastic T-cell lymphoma, extranodal NK/T-cell lymphoma nasal type, enteropathy- type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, cutaneous ?? T-cell lymphoma (excludes mycosis fungoides or Sézary syndrome), transformed mycosis fungoides, hepatosplenic T-cell lymphoma, ALCL (ALK-1 negative), or patients with ALK 1 expressing ALCL (ALK-1 positive) who have relapsed disease after ASCT; • Age =18 years; • Written informed consent (see Appendix A); • PD following at least one systemic therapy or refractory to at least one prior systemic therapy; • Measurable disease according to the IWC criteria (see Appendix B) and/or measurable cutaneous disease; • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix C); • Serum potassium =3.8 mmol/L and magnesium =0.85 mmol/L (magnesium converts to 2.0 mg/dl or 1.7 mEq/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 3 months 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • 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 C1D1 until study drug discontinuation) o Patients treated with a pulse of steroids must 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: o Congenital long QT syndrome; o QTc interval >480 milliseconds (msec); o Myocardial infarction within 6 months of 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 participate; o Other significant ECG abnormalities including 2nd° atrio-ventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). o Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see Appendix E). In any patient in whom there is doubt, the patient should be referred to a cardiologist for evaluation; o 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; o Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Appendix F) and/or ejection fraction <40% by MUGA scan or <50% by echocardiogram and/or MRI; o 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); o Hypertrophic cardiomyopathy or restrictive cardiomyopathy from prior treatment or other causes (if in doubt, see ejection fraction criteria above); o 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. o Any cardiac arrhythmia requiring anti-arrhythmic medication; • Serum potassium <3.8 mmol/L or serum magnesium <0.85 mmol/L (magnesium converts to 2.0 mg/dl or 1.7 mEq/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 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 involvi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to evaluate the activity of romidepsin in patients with progressive or relapsed PTCL following prior systemic therapy. The primary efficacy parameter is the rate of complete response, defined as the proportion of patients with complete response (CR) and unconfirmed complete response [CR(u)] according to the IWC for responses assessment for non-Hodgkin’s lymphomas (NHL).;Secondary Objective: • To estimate the rate of objective disease response (ORR), defined as the proportion of patients with CR, CR(u), and partial response (PR); • To estimate the duration of response, defined as the time from the first date of a disease response to the date of diagnosis of progressive disease (PD) or date of last study assessment if there is no disease progression; • To estimate the time to objective disease progression; • To assess tolerability and safety of romidepsin; and • To estimate the change in Eastern Cooperative Oncology Group (ECOG) performance status. ;Primary end point(s): • CR (Complete Response) : For the purposes of reviewing radiology, CR is defined as the complete disappearance of all radiographic evidence of disease. All large Nodal Index lesions (identified as abnormal lymph nodes or nodal masses > 15mm at baseline) must have decreased to =15 mm in their greatest diameter. All small Nodal Index lesions (identified as abnormal lymph nodes or nodal masses between 11mm and 15mm at baseline) must have decreased to =10 mm in their greatest diameter or,in aggregate, those lesions must have regressed >75% in their SPD compared to baseline. If the spleen or liver is considered to have been enlarged before therapy due to involvement by lymphoma, it must have regressed in size. Any macroscopic nodules detectable in any organs should no longer be present. • CR(u) (Complete Response unconfirmed): Includes all the criteria for CR listed above except that all Nodal Index lesions (large or small) must have regressed | — |
Countries
Czech Republic, France, Germany, Italy, Spain, Sweden, United Kingdom
Outcome results
None listed