A phase I/II study to find the safe dose of the combination of romidepsin and carfilzomib (phase I) in patients with relapsed or refractory T-Cell lymphoma. The phase II part of the study will look at the activity of the combination.
- Conditions
- Peripheral T-cell LymphomaMedDRA version: 20.0Level: PTClassification code 10034626Term: Peripheral T-cell lymphoma unspecified refractorySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10034625Term: Peripheral T-cell lymphoma unspecified recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001879-20-GB
- Lead Sponsor
- niversity of Birmingham
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 57
• Age = 16 years of age
• Life expectancy > 12 weeks
• ECOG performance status = 2
• Relapsed or refractory* peripheral T-cell lymphoma including the following histologies: peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, enteropathy associated T-cell lymphoma, extranodal NK/T-cell lymphoma, transformed mycosis fungoides, hepatosplenic T-cell lymphoma
• Failed at least 1 prior therapy (but no upper limit of prior regimens)
• Adequate haematopoietic reserve (Hb = 9g/dl, neutrophils = 1.0x109/l and platelets = 100x109/l or = 75x109/l if marrow involvement documented)
• Adequate liver function (bilirubin = 1.5 x ULN, AST / ALT = 2x ULN)
• Adequate renal function (creatinine clearance = 20ml/min as assessed by Cockcroft and Gault calculation)
• Serum potassium = 4.0 mmol/l, calcium = 2.2 mmol/l and magnesium = 0.85 mmol/l prior to trial entry
• CT measurable disease with at least 1 lesion having short axis > 1.5cm or splenomegaly > 14cm in cranio-caudal length attributable to relapsed lymphoma
• Ability to give informed consent
* For all relapsed patients, relapse must be confirmed by tissue biopsy (or bone marrow trephine if no other tissue available). For refractory patients, a biopsy must have been obtained within the last 6 months and preferably to confirm refractory disease.
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 22
• Persistent treatment related toxicities of CTCAE v4.0 grade = 2
• Previous treatment with histone deactylase inhibitor or proteasome inhibitor
• Need for any other concurrent anti-cancer drug (apart from corticosteroids at a dose equivalent to prednisolone = 7.5mg daily). A steroid prephase may be used but should be stopped by the first day of cycle 1.
• Concurrent medical illness deemed by the investigator as uncontrolled and/or clinically significant
• Co-existing active infection requiring parenteral antibiotics
• Patients unable to swallow oral medication
• Active infection with HIV, hepatitis B or hepatitis C
• Radiotherapy* (except for palliative reasons), endocrine therapy, immunotherapy or use of other investigational agents within 28 days prior to trial entry (or a longer period depending on the defined characteristics of the agents used, please contact the trials office for confirmation). *Limited field radiotherapy to an isolated lesion in bone or soft tissue must be completed 2 weeks prior to trial entry
• Major surgery within 4 weeks of trial entry
• Patients with proven CNS involvement
• QTc interval of = 480ms or patients taking medications that significantly prolong the QT interval (Appendix 7)
• Clinically significant cardiac disease = NYHA Class III, symptomatic ischaemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within 6 months of trial entry
• Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry and within 7 days prior to the start of treatment. Postmenopausal females (> 45 years old and without menstruation for > 1 year) and surgically sterilised females are exempt from a pregnancy test)
• Patients and partners of childbearing potential not willing to use effective contraception during and for 3 months after therapy
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method