Advanced Follicular Lymphoma MedDRA version: 20.0 Level: PT Classification code 10016910 Term: Follicle centre lymphoma, follicular grade I, II, III stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10016909 Term: Follicle centre lymphoma, foll
Conditions
Interventions
Trade Name: Truxima
Product Name: CT-P10
Product Code: CT-P10
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed
Sponsors
CELLTRION, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each patient must meet all of the following criteria to be enrolled in this study: 1. Patient is male or female 18 years or older. 2. Patient has histologically confirmed FL according to the World Health Organization 2008 classification (Jaffe 2009); grades 1 to 3a based on local laboratory review. 3. Patient has at least 1 measurable tumour mass that has not previously been irradiated, and the mass must be: • nodal lesion >15mm in the longest dimension; or • nodal lesion>10mm =15mm in the longest dimension and >10mm in the shortest dimension; or • extranodal lesion with both long and short dimensions =10mm. 4. Patient has confirmed CD20+ lymphoma, as assessed by local laboratory review. 5. Patient has Ann Arbor stage III or IV disease. 6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Oken 1982). 7. For both male and female patients and their partners of childbearing potential, patient agrees to practice total abstinence or to use one of the following medically acceptable methods of contraception during the course of the study and for 12 months following discontinuation of study treatment (excluding women who are not of childbearing potential and men who have been sterilised): • Barrier contraceptives (male condom, female condom or diaphragm with a spermicidal gel) • Hormonal contraceptives (implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings) • Intrauterine devices Male or female patients and their partners who have been surgically sterilised for less than 6 months prior to study entry must agree to use 1 medically acceptable method of contraception or practice total abstinence. Menopausal females must have experienced their last period more than 12 months prior to study entry (ie, when the informed consent form [ICF] is signed) to be classified as not of childbearing potential. 8. For both premenopausal women and women who are less than or equal to 12 months after the onset of menopause, patient has a negative serum pregnancy test during the Screening Period. 9. Patient has adequate bone marrow, hepatic, and renal function reserve as evidenced by: • Haemoglobin level of =8 g/dL • Absolute neutrophil count (ANC) of =1500/mm3 • Platelet count of =75 000/mm3 • Total bilirubin level of =2.0 mg/dL • Aspartate aminotransferase and alanine aminotransferase levels of =3 times the upper limit of normal (ULN) for the reference laboratory (=5 × ULN for the reference laboratory with known hepatic involvement by lymphoma) • A serum creatinine level of =1.5 × ULN for the reference laboratory, or a calculated creatinine clearance by the Cockcroft-Gault equation (Rostoker et al 2007) of =50 mL/min 10. Patient is able to understand verbal and/or written instructions and comply with all study requirements. 11. Patient is informed, given ample time and opportunity to read and/or understand about participation in the study, and has signed and dated the written ICF. Are the trial subjects under 18? no Number of subject
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria will be excluded from the study: 1. Patient has received rituximab (or a rituximab proposed biosimilar product), cyclophosphamide, or vincristine. 2. Patient has allergies or hypersensitivity to murine, chimeric, human or humanised proteins, cyclophosphamide, vincristine, or prednisone. 3. Patient has evidence of histological transformation to high-grade or diffuse large B-cell lymphoma. 4. Patient has known central nervous system involvement. 5. Patient has received previous treatment for NHL: • Previous treatment including chemotherapy, radiotherapy, immunotherapy, and/or surgery (except previous biopsy). However, patients who have received radiotherapy as part of the palliative therapy are eligible if the last fraction of radiotherapy was administered at least 4 weeks prior to Day 1 of Cycle 1 and patients must have recovered from all radiotherapy-related toxicities prior to randomisation. • All doses of corticoid therapy for treatment of NHL • Corticoid therapy during the previous 4 weeks from Day 1 of Cycle 1 with prednisone >20 mg per day for the treatment for any purpose 6. Patient has a current diagnosis of active tuberculosis (TB) (defined by chest x-ray, CT, or proper image) or other severe infections, such as sepsis, abscesses, or opportunistic infections. 7. Patient has a known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. (Carriers of hepatitis B are not permitted to enrol into the study.) 8. Patient has New York Heart Association class III or IV heart failure, severe uncontrolled cardiac disease (unstable angina, clinically significant electrocardiogram abnormalities), or myocardial infarction within the previous 6 months before the ICF is signed. 9. Patient has any malignancy other than NHL, except adequately treated squamous or basal cell carcinoma of the skin or cervical carcinoma in situ, within the previous 5 years before Day 1 of Cycle 1. 10. Patient has a current or recent (within 30 days before Day 1 of Cycle 1) treatment with any other investigational medicinal product or device. 11. Patient has uncontrolled diabetes mellitus, even after insulin treatment. 12. Patient is pregnant or lactating. Patients who are planning to be pregnant or to breastfeed before, during, or within 12 months after the last infusion of study treatment are not permitted to enrol into the study. 13. Patient is taking a live, live-attenuated, or nonlive vaccine within 4 weeks before Day 1 of Cycle 1 of study treatment. 14. Patient has evidence of any other coexisting disease or medical or psychological condition, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational product, or patient is a high risk for treatment complications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate that CT-P10 is: - similar to Rituxan in terms of pharmacokinetics as determined by area under the serum concentration-time curve at steady state (AUCtau) and maximum serum concentration at steady state (CmaxSS) at Cycle 4. - noninferior to Rituxan in terms of efficacy as determined by overall response rate (complete response [CR] + unconfirmed complete response [CRu] + partial response [PR]) over Cycle 8 (Core Study Period) according to the 1999 International Working Group (IWG criteria in previously untreated patients with advanced (stage III-IV) CD20+ FL. ; Secondary Objective: To evaluate additional pharmacokinetics, efficacy parameters, pharmacodynamics, overall safety, and biomarkers of CT-P10 in comparison with Rituxan during the Core Study Period, Maintenance Study Period, and Follow-up Period. To evaluate pharmacodynamics (B-lymphocyte [B-cell] kinetics, including depletion and recovery), overall safety, efficacy and biomarkers of CT-P10 in comparison with Rituxan. (Part 1). ; Primary end point(s): - PART 1: Pharmacokinetics: the primary endpoints will be AUCtau and CmaxSS - PART 2: Efficacy: the primary endpoints will be overall response rate (CR + CRu + PR) according to the 1999 International Working Group (IWG) ; Timepoint(s) of evaluation of this end point: - PART 1: Pharmacokinetics: in the Core Study Period (12 weeks) of study treatment - PART 2: Efficacy: 8 cycles in the Core Study Period (24 weeks) of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - PART 1: Pharmacokinetics: 4 cycles in the Core Study Period of study treatment. - PART 2: 8 cycles in the Core Study Period (24 weeks) of study treatment. ; Timepoint(s) of evaluation of this end point: - PART 1: Pharmacokinetics: 4 cycles in the Core Study Period of study treatment - PART 2: Efficay: secondary endpoints include additional efficay parameters, pharmacodynamics and safety during the Core Study Period, Maintenance Study Period, and Follow-up Period | — |
Countries
Belarus, Brazil, Bulgaria, Chile, Georgia, Greece, India, Italy, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, South Africa, Spain, Turkey, Ukraine
Contacts
Public ContactReg Affairs & Clinical Operation
CELLTRION, Inc
Outcome results
None listed