Low Tumour Burden Follicular Lymphoma. MedDRA version: 20.0 Level: PT Classification code 10065856 Term: Non-Hodgkin's lymphoma unspecified histology indolent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
CELLTRION, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient is male or female =18 years. 2. Patient has histologically confirmed CD20+ FL grade 1 to 3a according to the World Health Organization 2008 classification (Jaffe et al 2009); biopsy within 6 months before the first administration of the study drug. 3. Patient has at least 1 measurable tumour mass in 2 dimensions, and the mass must be: • Nodal lesion >15 mm in the longest dimension; or • Nodal lesion >10 mm to =15 mm in the longest dimension and >10 mm in the shortest dimension; or • Extranodal lesion with both long and short dimensions =10 mm 4. Patient has Ann Arbor stage II, III, or IV disease. 5. Patient has low tumour burden, defined as based on Groupe d'Etudes des Lymphomes Folliculaires (GELF) criteria: • No B symptoms, • LDH < upper limit of normal (ULN), • Largest nodal or extra mass <7 cm, • <3 nodal sites with a diameter =3 cm, • No significant serous effusions detectable clinically or on CT (small, clinically non-evident effusions on CT scan are not deemed significant), • Spleen =16 cm by CT, and • No clinical organ failure or organ compression (e.g. ureteric obstruction) 6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Oken et al 1982). 7. For both male and female patients and their partners of childbearing potential, patient agrees to practice true abstinence (when this is in line with preferred and usual lifestyle of the subject) 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 drug (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 the first administration of the study drug must agree to use 1 medically acceptable method of contraception or practice true abstinence during study treatment. 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. 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. 8. Patient has adequate bone marrow, hepatic, and renal function reserve as evidenced by: • Haemoglobin level of =10 g/dL • Absolute neutrophil count of =1500/mm3 • Platelet count of =100 000/mm3 • Total bilirubin level of =2.0 mg/dL • Aspartate aminotransferase and alanine aminotransferase levels of =3 times the ULN for the reference laboratory (=5 × ULN for the reference laboratory with known hepatic involvement by lymphoma)
Exclusion criteria
Exclusion criteria: 1. Patient has received rituximab (or a rituximab proposed biosimilar product). 2. Patient has allergies or hypersensitivity to contrast agents for radiograph, murine, chimeric, human or humanised proteins. 3. Patient has evidence of histological transformation to high-grade or diffuse large B-cell lymphoma. 4. Patient has known central nervous system involvement or any evidence of spinal cord compression by lymphoma. 5. Patient has received previous treatment for NHL: • Previous treatment including chemotherapy, radiotherapy, immunotherapy, and/or surgery (except previous biopsy). • All doses of corticoid therapy for treatment of NHL. • Corticoid therapy within 4 weeks before the first administration of the study drug, with prednisone >20 mg per day (or equivalent doses of other steroid medications) for any purpose except NHL. 6. Patient has a severe infection, such as sepsis, abscesses, active tuberculosis (TB), or opportunistic infections. 7. Patient has a known infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C (carriers of hepatitis B and hepatitis C are not permitted to enrol into the study). 8. Patient has New York Heart Association (Raphael et al 2007) class III or IV heart failure, severe uncontrolled cardiac disease (unstable angina, clinically significant electrocardiogram [ECG] abnormalities), or myocardial infarction within the previous 6 months before the first administration of the study drug. 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 5 years before the first administration of the study drug. 10. Patient has a current or recent treatment (within 42 days before the first administration of the study drug or 5 times the half-life, whichever is longer, prior to screening) 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 administration of the study drug are not permitted to enrol into the study. 13. Patient is taking a live, live-attenuated, or nonlive vaccine within 4 weeks before the first administration of the study drug. 14. Patient has evidence of any other coexisting disease or medical or psychological condition, metabolic dysfunction, unstable pulmonary condition, 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 high risk for treatment complications at the investigator’s discretion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Overall response rate (CR + CRu + PR) at 7 months (Prior to Cycle 3 of Maintenance Study Period), according to the Modified Response Criteria for Malignant Lymphoma.;Timepoint(s) of evaluation of this end point: At 7 months (Prior to Cycle 3 of Maintenance Study Period).;Main Objective: To demonstrate that CT-P10 is similar to Rituxan in terms of efficacy as determined by overal response rate [ORR] (complete response [CR] + unconfirmed complete response [CRu] + partial response [PR]) at 7 months (Prior to Cycle 3 of Maintenance Study Period) according to the Modified Response Criteria for Malignant Lymphoma.; Secondary Objective: • To evaluate ORR (CR + CRu + PR) according to the Modified Response Criteria for Malignant Lymphoma during the study period. • To evaluate additional efficacy parameters (progression-free survival, time to progression and overall survival according to the Modified Response Criteria for Malignant Lymphoma). • To evaluate pharmacokinetics, pharmacodynamics (B-lymphocyte [B-cell] kinetics), overall safety including immunogenicity, and biomarkers of CT-P10 in comparison with Rituxan. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Endpoints will be assessed during the whole study till Follow-up visit (Day 1 of Cycle 1 of the Induction Study Period and Day 1 of Cycles 1-2 and Day 1 of Cycle 2-4, during Maintenance Study Period, and Follow-up Period). Please note not all endpoints will be assessed on each of the visits.; Secondary end point(s): - The following efficacy parameters for the study drug will be determined as secondary endpoints: • Overall response rate (CR + CRu + PR) during the study period according to the Modified Response Criteria for Malignant Lymphoma • Progression-free survival, defined as the interval between randomisation and disease progression/relapse, or death from any cause, whichever occurs first • Time to progression, defined as the interval between randomisation and disease progression/relapse or death as a result of lymphoma, whichever occurs first • Overall survival, defined as the interval between randomisation and death from any cause - The following pharmacokinetic (PK) parameters for the study drug will be determined as secondary endpoints: • Maximum serum concentration (Cmax) at each dose • Trough serum concentration (Ctrough) at each dose - The secondary pharmacodynamic (PD) endpoint is B-cell kinetics. - The safety endpoints will be assessed using the following: AEs, SAEs, concomitant medications, hypersensitivity (via vital signs monitoring including systolic and diastolic BP, heart rate, respiratory rate, and body temperature), physical examination findings, vital signs measurements, clinical laboratory analyses, chest x ray findings, ECG findings, infection, infusion related reactions, immunogenicity testing, immunoglobulin testing, and TB assessment. - The biomarker endpoints: the Fc?R genotype (Fc?RIIa, IIIa, and/or any neces | — |
Countries
Australia, Belarus, Brazil, Chile, Czech Republic, Georgia, India, Israel, Italy, Japan, Korea, Republic of, Latvia, Malaysia, Mexico, Peru, Poland, Portugal, Romania, Russian Federation, Spain, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
Public ContactMinJi Ma- Clinical Operation
CELLTRION, Inc.
Outcome results
None listed