Cutaneous T-cell lymphoma (CTCL), (peripheral T-cell lymphoma unspecified NOS)
Conditions
Interventions
Product Name: Depsipeptide
Product Code: FK228
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: not yet given
Current Sponsor code: FK228
Other descriptive name:
Sponsors
Gloucester Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Males or non-pregnant females aged ?18 years. • Histologically confirmed diagnosis of CTCL, including mycosis fungoides and Sézary syndrome. • Patients with CTCL stages IIa, IIb, III and IVa • Patients with CTCL stage Ib who have relapsed following previous therapy and where, in the investigator’s opinion, the potential benefit of treatment with FK228 outweighs the possible risks. • Patients who have failed standard skin-directed therapy and have had at least one course of systemic therapy, such as interferon, which they have been deemed to have failed. • Anticipated life expectancy greater than six months. • Written informed consent to participate in the study. 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: • ECOG Performance Status > 1 (see Appendix H). • Patients who have not received at least 1 course of prior systemic therapy for CTCL. • Visceral involvement i.e. Stage 4b disease (lymphadenopathy is allowed). • Patients with known cardiac abnormalities such as:- Congenital long QT syndrome QTc interval > 480 milliseconds Any cardiac arrhythmia requiring anti-arrhythmic medication. • Patients who have had a myocardial infarction within 12 months of study entry. • Patients who have a history of coronary artery disease (CAD) e.g. angina Canadian class II to IV (Appendix N). In any patient in whom there is doubt, the patient should have a stress imaging study and exercise ECG and, if abnormal, angiography to define whether or not CAD is present. • Patients with an ECG recorded at screening showing evidence of cardiac ischaemia (ST depression of ?2 mm). If in any doubt, the patient should have a stress imaging study and exercise ECG and, if abnormal, angiography to define whether or not CAD is present. • Patients with congestive heart failure that meets New York Heart Association class II to IV definitions (Appendix O) and/or ejection fraction 1.25 x upper limit of normal (ULN) for institution; o aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamic pyruvic transaminase (ALT/SGPT) >2.0 x ULN, serum creatinine >2 x ULN for age and sex. • Coexistent second malignancy or history of prior malignancy within previous 5 years (excluding basal or squamous cell carcinoma of the skin or cervical epithelial neoplasm [CIN1, carcinoma in situ] that has been treated curatively). • Any significant medical or psychiatric condition that might prevent the patient from complying with all study proced
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The rate of objective disease control as defined as confirmed complete response (CR), complete clinical response (CCR), partial response (PR), or stable disease (SD, for SD with a duration of at least 3 months) as determined by the Objective Primary Disease Response Evaluation Criteria (OPDREC);Main Objective: To confirm the efficacy of FK228, depsipeptide, as reported in the Phase I and early Phase II studies, in patients with CTCL who are no longer controlled on skin-directed therapy and who have had at least one prior systemic therapy. The rate of objective disease control, as determined by Objective Primary Disease Response Evaluation Criteria (OPDREC) will be used as the primary endpoint to assess efficacy.;Secondary Objective: To evaluate duration and durability of objective disease response, and time to objective disease progression. To evaluate the safety of FK228 in terms of adverse events, clinical laboratory data, physical examinations, ECG findings, rate of neutropenic fever and sepsis, blood transfusions, and treatment compliance. To evaluate the pharmacokinetics of FK228 in a cohort of patients with CTCL. To evaluate disease status with molecular markers in PBMCs and potentially tumours, including acetylation status, apoptosis markers, STAT, AKT, and caspases. | — |
Countries
Austria, Germany, United Kingdom
Outcome results
None listed