A multicentre open-label, dose-escalation, trial of zanolimumab in combination with CHOP chemotherapy in subjects with CD4 positive non-cutaneous peripheral T-Cell Lymphoma with nodal involvement - Zanolimumab with CHOP in CD4+ non-cutaneous PTCL with nodal involvment

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-004516-51-IT
• Date of registration: 17/05/2007
• Prospective Registration: No
• Primary sponsor: SERONO INTERNATIONAL SA
• Public title: A multicentre open-label, dose-escalation, trial of zanolimumab in combination with CHOP chemotherapy in subjects with CD4 positive non-cutaneous peripheral T-Cell Lymphoma with nodal involvement - Zanolimumab with CHOP in CD4+ non-cutaneous PTCL with nodal involvment
• Scientific title: A multicentre open-label, dose-escalation, trial of zanolimumab in combination with CHOP chemotherapy in subjects with CD4 positive non-cutaneous peripheral T-Cell Lymphoma with nodal involvement - Zanolimumab with CHOP in CD4+ non-cutaneous PTCL with nodal involvment
• Date of first enrolment: 20/12/2006
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004516-51
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Germany, Italy, Netherlands

Key inclusion & exclusion criteria

Inclusion criteria:
1. Non-cutaneous peripheral T-cell lymphoma, with nodal involvement, with a CD4 positive phenotype confirmed by biopsy that must be performed within 2 months of Screening (node involvement must be accessible and measurable) excluding ALK + ALCL 2. Subjects must be eligible for the CHOP chemoterapy regimen. 3. Subjects may have had no more than one previous chemotherapy, excluding anthracyclines, and must have been in remission ofr at least one year. 4. Measurable disease according to the Standardized Response Criteria for NHL 5. Age major/equal 18 years 6. Has read and understands and has signed the informed consent (or has a legally acceptable representative who has signed on theri behalf) 7. Subjects and their partners will be requested to use medically approved contraception (e.g. intra-uterine device, diaphragm, condom with spermicides, contraceptive medication) from signature of informed consent until 8 weeks after the end of the last 3-week Cycle of CHOP. Exception: women who are psotmenopausal for more than 2 years; subjects who are surgically sterile or have a partner who is surgically sterile. 8. ECOG performance status minor/equal 2.
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:
1. Known or suspected hypersensitivity to CHOP or components of the IMP 2. Known infection with HIV, unresolved hepatitis C (HCV RNA + in plasma) or hepatitis B (HBV DNA+, HBs Ag+, HBc Ag+), signs and symptoms of transmissible spongiform encepalopathy 3. Other concurrent or previous malignancies within the past 5 years, except adequately treated in situ carcinoma of the uterine cervix or basal cell carcinoma 4. Significant concurrent, uncontrolled or active medical condition including, but not limited to acute or chronic infectious disease requiring systemic medication renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral or psychiatric disease. 5. Known or clinical suspicion for CNS involvement of the PTCL with nodal involvement 6. Severe bone marrow impariment as evidenced by Hemoglobin (Hb) < 9.0 g/dL, asbolute neutrophil count (ANC) < 0.5 x 109/l, plateletes < 20 x 109/l at Screening 7. Subjects having received extensive radiotherapy (involving major/equal 30% of bone marrow) within the last 2 years 8. Renal impairment as evidenced by serum creatinine > 1.5 x upper limit of normal (ULN), and/or calculated creatinine clearance < 60 ml/min at Screening. 9. Liver function abnormality as defined by total bilirubin > 1.5 ULN and/or AST/ALT > 2.5 x ULN or for subjects with liver involvement AST/ALT > 5 x ULN 10. INR > 1.5 x ULN at Screening 11. Breast-feeding woment or women with a positive pregnancy test at Screening 12. Any immunosuppressive or cytotoxic drugs within 3 months from Screening (e.g. drugs interfering with the functions of T cell, IL-2, etc) 13. Prior treatment with anti-CD4 monoclonal antibodies within one year prior to Screening


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

Health Condition(s) or Problem(s) studied

CD4 positive non cutaneous peripheral T-Cell lymphoma with nodal involvement
MedDRA version: 9.1 Level: LLT Classification code 10034623 Term: Peripheral T-cell lymphoma unspecified

Intervention(s)

Product Name: zanolimumab
Pharmaceutical Form: Solution for infusion
Current Sponsor code: HuMax-CD4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): The number of subjects experiencing a Dose-Limiting Toxicity related to study drug during the first Cycle of CHOP in each cohort

Main Objective: To investigate safety and tolerability of ascending doses of zanolimumab up to 20 mg/kg in combination with CHOP chemotherapy in order to define a maximum tolerated dose (MTD) in subjects with CD4 positive non-cutaneous peripheral T-Cell Lymphoma with nodal involvement

Secondary Objective: - Assess the pharmacokinetic (PK) profile of zanolimumab and doxorubicin when zanolimumab is administered concomitantly with CHOP; - Assess pharmacodynamic (PD) parameters in order to look for associations with PK, tolerability and efficacy signals. Tumore metabolic activity will be measured in a subset of subjects (centers with PET scanners) - Investigate efficacy signals (CR, CRu, PR) - Investigate host immune response to zanolimumab administration - To explore changes in CD4 positivity in subjects with biopsy for progressive disease

Secondary ID(s)

2006-004516-51-NL

27056