A clinical study to determine whether a new drug masitinib is safe and effective in cancer of the white blood cells.

• Register: EUCTR
• Last refreshed on: 3 August 2020
• Main ID: EUCTR2010-021091-28-GB
• Date of registration: 16/12/2014
• Prospective Registration: No
• Primary sponsor: AB Science
• Public title: A clinical study to determine whether a new drug masitinib is safe and effective in cancer of the white blood cells.
• 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. - Phase2/3 of masitinib+dexamethasone & gemcitabine in TCell lymphoma v1
• Date of first enrolment: 10/11/2014
• Target sample size: 267
• Recruitment status: Not Recruiting
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, France, Germany, Greece, Hungary, India, Italy, Korea, Democratic People's Republic of, Malaysia, Philippines, Romania, Serbia, Singapore, Slovakia, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Project Manager
• Affiliation: AB Science

• Name: Clinical Project Manager
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient with histologically/cytologically confirmed peripheral T-cell lymphoma (PTCL), using the 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 to 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 and 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)
- Albuminaemia > 1 x LLN
- Proteinuria < 30 mg/dl (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. Female patient of childbearing potential (entering the study after a menstrual period and who has a negative pregnancy test), who agrees to use a highly effective method of contraception and an acceptable method of contraception by her male partner during the study and for 3 months after the last treatment intake.

Male patient with a female partner of childbearing potential who agrees to use a highly effective method of contraception and an acceptable method of contraception by his female partner during the study and for 3 months after the last treatment intake OR who agrees to use an acceptable method of contraception and a highly effective method of contraception by his female partner during the study and for 3 months after the last treatment intake.

Highly effective methods of contraception include:
­-Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
­-Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable,or implantable
­-Intrauterine device (IUD)
­-Intrauterine hormone-releasing system (IUS)
­-Bilateral tubal occlusion
­-Vasectomized male (azoospermia assessed medically)
­-Sexual abstinence (Its reliability should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient)
Acceptable methods of contraception include:
­-Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
­-Male or female condom with or without spermicide
­-Cap, diaphragm or sponge with spermicide
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 symp
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:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- 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 (atrioventricular block 2 and 3, sino-atrial block)
- Syncope without known aetiology within 3 months
- Uncontrolled severe hypertension, according to the judgment 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 a 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
11. Patients requiring medication, which are prohibited in the current protocol, including anticancer drugs other than masitinib and gemcitabine, corticosteroids other than dexamethasone, investigational drugs, live attenuated vaccines, drugs known to be at high risk of Stevens-Johnson or DRESS syndrome.

Washout:
- Patient with a major surgery or radiation therapy within four weeks of starting the study treatment
- Treatments with an investigational agent or anti-tumour 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] - Cancer [C04]

Relapsed or refractory peripheral T-cell lymphoma
MedDRA version: 18.1 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)
MedDRA version: 18.1 Level: PT Classification code 10034623 Term: Peripheral T-cell lymphoma unspecified System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Masitinib mesylate
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib
CAS Number: 790-299-795
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: Masitinib mesylate
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Masitinib
CAS Number: 790-299-795
Current Sponsor code: AB1010
Other descriptive name: MASITINIB MESYLATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Gemcitabine
Product Name: Gemcitabine
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1000-

Trade Name: Dexamethasone
Product Name: Dexamethasone
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: Secondary objectives are to evaluate the complementary efficacy (Progression Free Survival and Tumor Response) and safety in each treatment group of patients with relapsed or refractory peripheral T-cell lymphoma:
- masitinib at 6 mg/kg/day in combination with dexamethasone
- dexamethasone in combination with gemcitabine
- masitinib at 6 mg/kg/day in combination with dexamethasone and gemcitabine

Main Objective: The objective is to evaluate the efficacy and safety of masitinib at 6 mg/kg/day in combination with dexamethasone, dexamethasone in combination with gemcitabine and the combination of masitinib at 6 mg/kg/day, dexamethasone and gemcitabine in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).

Primary end point(s): Overall Survival (OS) defined as time from randomisation until death due to any cause.

Timepoint(s) of evaluation of this end point: Time of death

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Efficacy:
Survival rate at Weeks 12, 24 and then every 24 weeks;
Progression Free Survival (PFS) rates at Weeks 12, 24, and then every 24 weeks;
Overall Time to Progression (TIP) and TIP rate at Weeks 12, 24, and then every 24 weeks;
Response rate at Weeks 12, 24, and then every 24 weeks, including documenting best response rate and duration during study treatment;
Clinical benefit defined as time to reappearance or progression of lymphoma- related symptoms every 4 weeks until Week 24 and then every 12 weeks.

Secondary end point(s): Efficacy:
Survival rates at W12, W24 and then every 24 weeks;
Overall Progression Free Survival (PFS)
Progression Free Survival (PFS) rates at W12, W24 and then every 24 weeks;
Overall Time to Progression (TTP);
TTP rate at W12, W24 and then every 24 weeks;
Response rate at W12, W24 and then every 24 weeks;
Best response rate during study treatment;
Duration of response;
Clinical benefit defined as time to reappearance or progression of lymphoma-related symptoms every 4 weeks until W24 and then every 12 weeks;
Time to next PTCL treatment.
Pain improvement (VAS)
Pharmacogenomic assessment : Relationship between genomic data and overall survival
Pharmacokinetics study (in group 1 – French patients only) to evaluate a potential interaction of dexamethasone on masitinib pharmacokinetic parameters.
Safety profile in each group using the NCI CTCAE v4.03 classification.
Other analysis:

Secondary ID(s)

AB10004

113,719

2010-021091-28-CZ

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date: 29/07/2014
Contact: