A study to compare masitinib with dexamethasone and gemcitabine in the treatment of patients with relapsed or refractory peripheral T-cell lymphoma

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2010-021091-28-HU
• Date of registration: 07/01/2015
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: A study to compare masitinib with dexamethasone and gemcitabine in the treatment of patients with relapsed or refractory peripheral T-cell lymphoma
• Scientific title: A multicenter, randomised, open-label, three-parallel groups, phase 2-3 study to evaluate the efficacy and safety of masitinib with dexamethasone, gemcitabine with dexamethasone and the combination of masitinib, gemcitabine and dexamethasone in patients with relapsed or refractory peripheral T-cell lymphoma
• Date of first enrolment: 22/04/2015
• Target sample size: 255
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021091-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Austria, China, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Italy, Korea, Republic of, Malaysia, Philippines, Romania, Russian Federation, Serbia, Singapore, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States

Contacts

• Name: Bence Kelemen
• Affiliation: Hungarotrial Zrt.

• Name: Bence Kelemen
• Affiliation: Hungarotrial Zrt.

Key inclusion & exclusion 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 < 2
6. Patients with adequate organ function
• Absolute neutrophils count (ANC) = 1.5 x 109/L, or = 1 x 109/L in case of medullary involvement
• Haemoglobin = 10 g/dL
• Platelets (PTL) = 75 x 109/L
• AST/ALT = 3x ULN (= 5 x ULN in case of liver metastases)
• Gamma GT = 2.5 x ULN (= 5 x ULN in case of liver metastases)
• Bilirubin = 1.5x ULN (= 3xULN in case of liver metastases)
• Normal Creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
• Albumin > 1 x LLN
• Proteinuria < 30 mg/mL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
7. Patient with life expectancy > 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:
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

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)

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): •Overall survival (OS) defined as the time from randomisation to the date of death due to any cause.

Main Objective: Overall Survival (OS)

Timepoint(s) of evaluation of this end point: the time from randomisation to the date of death

Secondary Objective: • 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
o Cytidine Deaminase Activity
o Pharmacogenomic analysis:
• Pharmacokinetics study (in group 1)

Secondary Outcome(s)

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

Secondary ID(s)

2010-021091-28-GR

AB10004

Source(s) of Monetary Support

AB Science