Relapsed or refractory Peripheral T-cell lymphoma MedDRA version: 17.1 Level: PT Classification code 10061871 Term: Non-Hodgkin's lymphoma transformed recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AB Science
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient with histologically/cytologically confirmed peripheral T-cell lymphoma (PTCL), using the World Health Organisation (WHO) disease classification 2008: • Adult T-cell lymphoma/leukemia (human T-cell leukemia virus [HTLV] 1+) • Angioimmunoblastic T-cell lymphoma • Anaplastic large cell lymphoma ALK+ • Anaplastic large cell lymphoma ALK- • Peripheral T-cell lymphoma - NOS (not otherwise specified) • Extranodal Natural Killer (NK)/T-cell lymphoma • Enteropathy-associated T-cell lymphoma • Hepatosplenic T-cell lymphoma • Subcutaneous panniculitis T-cell lymphoma • Transformed mycosis fungoides 2. Patient with documented progression of disease after at least 1 previous chemotherapy cycle 3. Patient with minimum 1 bidimensionally measurable disease (more than 1.5 cm) according the Cheson criteria 4. Patient having Ann Arbor stage II–IV 5. Patient with ECOG Performance Status 1 x LLN • Proteinuria 3 months 8. Man or woman, age = 18 years 9. Body mass index > 18 and body weight > 40 kg 10. Man and woman of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test) must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake. 11. Patient able and willing to comply with study procedures as per protocol. 12. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment. 13. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent. 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 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: 1. Patient with: • T-cell prolymphocytic leukemia • T-cell large granular lymphocytic leukemia • Mycosis fungoides, other than transformed mycosis fungoides • Sezary syndrome • Primary cutaneous CD30+ T-cell lymphoproliferative disorders 2. Patient with central nervous involvement of lymphoma 3. Patient with previous allogeneic stem cell transplantation 4. Patient who relapsed less than three months after an autologous stem cell transplantation 5. Patient presenting with cardiac disorders defined by at least one of the following conditions: • Patient with recent cardiac history (within 6 months) of: o Acute coronary syndrome o Acute heart failure (class III or IV of the NYHA classification) o Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death) • Patient with cardiac failure class III or IV of the NYHA classification • Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block) • Syncope without known aetiology within 3 months • Uncontrolled severe hypertension, according to the judgement of the investigator, or symptomatic hypertension 6. Patient with clinically uncontrolled infectious diseases and patient with Human Immunodeficiency Virus infection and/or hepatitis B or C infection 7. Patient with history of any other malignancy within the 5 years prior to study treatment, except carcinoma in situ of the cervix or basal cell carcinoma of the skin 8. Pregnant or nursing woman 9. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent 10. Patient with known hypersensitivity to gemcitabine and/or excipients WASHOUT • Patient with a major surgery or radiation therapy within four weeks of starting the study treatment • Treatments with an investigational agent or anti-tumor therapy (any chemotherapy, radiotherapy, immunotherapy or biologic agent) within 4 weeks prior to baseline • Treatment with corticosteroids within 7 days prior to baseline (except prednisone at a maximal dose of 0.5 mg/kg/day for less than 1 month) • Patients to be treated with gemcitabine will require a delay of at least four weeks between radiotherapy and the start of their treatment with gemcitabine.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Overall Survival (OS);Secondary Objective: •Efficacy: oSurvival rates at W12, W24 and then every 24 weeks oOverall Progression Free Survival (PFS) oProgression Free Survival (PFS) rates at W12, W24 and then every 24 weeks oOverall Time to Progression (TTP) o TTP rate at W12, W24 and then every 24 weeks oResponse rate at W12, W24 and then every 24 weeks oBest response rate during study treatment oDuration of response oClinical benefit defined as time to reappearance or progression of lymphoma-related symptoms every 4 weeks until W24 and then every 12 weeks oTime to next PTCL treatment •Safety profile in each group using the NCI CTCAE v4.03 classification •Other analysis: oExpression analysis oCytidine Deaminase Activity oPharmacogenomic analysis: •Pharmacokinetics study (in group 1) ;Primary end point(s): •Overall survival (OS) defined as the time from randomisation to the date of death due to any cause. ;Timepoint(s) of evaluation of this end point: the time from randomisation to the date of death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Efficacy: o Survival rates at W12, W24 and then every 24 weeks o Overall Progression Free Survival (PFS) o Progression Free Survival (PFS) rates at W12, W24 and then every 24 weeks o Overall Time to Progression (TTP) o TTP rate at W12, W24 and then every 24 weeks o Response rate at W12, W24 and then every 24 weeks o Best response rate during study treatment o Duration of response o Clinical benefit defined as time to reappearance or progression of lymphoma-related symptoms every 4 weeks until W24 and then every 12 weeks o Time to next PTCL treatment • Safety profile in each group using the NCI CTCAE v4.03 classification • Other analysis: o Expression analysis: Expression of c-Kit, PDGFR, tryptase, DCK (Deoxycytidine kinase) and other markers realized on tumour tissue before study treatment to evaluate the association with efficacy and/or toxicity of study treatment. o Cytidine Deaminase Activity in blood to evaluate the association with efficacy and/or toxicity to study treatment including gemcitabine. o Pharmacogenomic analysis: DNA analysis, studying gene amplification, deletion or mutation focused on genes involved in proliferation/survival pathways and genes involved in metabolism of gemcitabine, will be studied on tumor biopsy and/or blood to evaluate association with efficacy and/or toxicity of study treatment. • Pharmacokinetics study (in group 1) to evaluate a potential interaction of dexamethasone on masitinib pharmacokinetic parameters.;Timepoint(s) of evaluation of this end point: see section E.5.2 | — |
Countries
Austria, China, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Korea, Republic of, Malaysia, Philippines, Romania, Russian Federation, Serbia, Singapore, Slovakia, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactAlain Moussy
AB Science
Outcome results
None listed