CD4 positive non-cutaneous peripheral T-Cell Lymphoma with nodal involvement MedDRA version: 8.1 Level: LLT Classification code 10034624 Term: Peripheral T-cell lymphoma unspecified NOS
Conditions
Interventions
Product Name: zanolimumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: zanolimumab
CAS Number: 652153-01-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equa
Sponsors
Genmab A/S
Eligibility
Sex/Gender
All
Inclusion 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 chemotherapy regimen. 3. Subjects may have had no more than one previous chemotherapy, excluding anthracyclines, and must have been in remission for at least one year. 4. Measurable disease according to the Standardized Response Criteria for NHL 5. Age = 18 years. 6. Has read and understands and has signed the informed consent (or has a legally acceptable representative who has signed on their behalf). 7. Women of childbearing potential (i.e all female patients after puberty unless they are post-menopausal for at least two years, are surgically sterile or are sexually inactive) must have a negative pregancy test at screening. 8. Women of childbearing potential and males with female partners of childbearing potential must be willing to avoid pregancy by using an adequate method of contraception (defined as two barrier methods, or one barrier method with a spermicide, or intrauterine device or use of the oral female contraceptive) for 4 weeks prior to and during the study and 8 weeks after the end of the last 3 week cycle of CHOP). 9. ECOG performance status = 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
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 impairment as evidenced by Hemoglobin (Hb) 1.5 x upper limit of normal (ULN), and/or calculated creatinine clearance 1.5 ULN and/or AST/ALT > 2.5x ULN or for subjects with liver involvement AST/ALT > 5x ULN. 10. INR > 1.5 x ULN at Screening. 11. Breast-feeding women 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 cells, IL-2, etc.) 13. Prior treatment with anti-CD4 monoclonal antibodies within one year prior to Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate safety and tolerability of ascending doses of zanolimumab up to 20mg/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: 1. Assess the pharmacokinetic (PK) profile of zanolimumab and doxorubicin when zanolimumab is administered concomitantly with CHOP 2. Assess pharmacodynamic (Pd) parameters in order to look for associations with PK, tolerability and efficacy signals. Tumor metabolic activity will be measured in a subset of subjects (centers with PET scanners). 3. Investigate efficacy signals (CR, CRu, PR) 4. Investigate host immune response to zanolimumab administration 5. To explore changes in CD4 positivity in subjects with biopsy for progressive disease.;Primary end point(s): The number of subjects experiencing a Dose-Limiting Toxicity (DLT) related to study drug during the first Cycle of CHOP in each cohort. | — |
Countries
Germany, Italy, Netherlands
Outcome results
None listed