Low tumour burden follicular lymphoma MedDRA version: 20.0 Level: PT Classification code 10003899 Term: B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Recombinant Human-Mouse Chimeric Anti-CD20 Monoclonal Antibody Injection
Product Code: HLX01
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS
Sponsors
Shanghai Henlius Biotech Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Voluntary written informed consent before any study-related activities; 2. = 18 years of age; 3. Histologically-confirmed, stage II to IV non-Hodgkin lymphoma (NHL) (CD20+ FL of grades 1, 2, or 3a) by World Health Organization classification of lymphoid neoplasms (2016 revision); 4. Low tumour burden according to the GELF criteria: - No nodal or extranodal involvement of more than 7 cm in diameter; - Less than 3 masses >3 cm; - No B symptoms: B symptoms are defined as patients with lymphoma having one of the following symptoms: 1. Fever with a temperature >38? for 3 consecutive days 2. Weight loss without trying, exceeding 10% of body weight in 6 months 3. Drenching night sweats - No splenomegaly: spleen =16 cm by computed tomography (CT) scan - No complications such as ascites or organ compression - No pleural or peritoneal serous effusions - No leukaemic phase: 1.5 cm or extranodal lesion >1 cm in its longest diameter by CT scan as defined by the Modified Lugano Response Classification 2014; 8. Adequate organ function: - Creatinine clearance =50 ml/minute as assessed by the Cockcroft-Gault formula - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 × upper limit of normal (ULN); - Alkaline phosphatase (ALP) =2.5 × ULN; - Bilirubin =1.5 × ULN (=2 × ULN if hyperbilirubemia is due to Gilbert’s syndrome or haemolysis) 9. Women of childbearing potential (WOCBP) or male patients whose sexual partners are WOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study. For male patients, reliable methods of contraception should be used from the start of study drug treatment and for at least 12 months after the last study drug administration. For female patients, reliable methods of contraception should be used from at least 1 month before the start of study drug treatment and for at least 12 months after last study drug administration. Highly effective methods of contraception: - Combined (containing oestrogen and progestogen) hormonal contraception associated with inhibition of ovulation (administration may be oral, intravaginal, or transdermal); - Progestogen-only hormonal contraception associated with inhibition of ovulation (administration may be oral, injectable, or implantable) - Intrauterine device; - Intrauterine hormone-releasing system; - Bilateral tubal ligation or occlusion; - Vasectomy (provided that the male has a medical assessment of surgical success); - Sexual abstinence (defined as refraining from heterosexual intercourse during the entire period of risk in relation to the duration of the clinical study, in line with the preferred and usual lifestyle of the patient); 10. Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the Investigator and to comply with the requirements of the entire study. 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 159 F.1.3 Elderly (>=65 years) yes F.1.3
Exclusion criteria
Exclusion criteria: 1. Prior treatment for FL. Patients previously treated with radiotherapy for stage I FL may be eligible provided they have a measurable lesion located outside the radiation field; 2. Transformation to high-grade lymphoma; 3. Patients with advanced disease that are considered for treatment with combined chemo-immunotherapy; 4. Presence or history of central nervous system (CNS) lymphoma involvement; 5. Treatment with an investigational agent within 28 days of the first dose of study drug infusion; 6. Prior treatment with a chimeric antibody, including HLX01 and Mabthera®; 7. History of another malignancy within 2 years of screening, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ of the uterine cervix, breast or bladder, localised prostate cancer stage T1c or less – and provided that the patient remains relapse free; 8. Major surgery within 28 days of the first dose of study drug infusion (excluding lymph node biopsy); 9. Known human immunodeficiency virus (HIV) infection (Serological test for HIV should be performed at screen unless prohibited by local regulations); 10. Active and/or severe infections, including any ongoing infection requiring IV anti-microbial treatment; 11. Have a current diagnosis of active tuberculosis; 12. Active hepatitis B (HBV) and a positive serological test for HBV (except seropositive due to HBV vaccination) or hepatitis C virus (HCV); 13. Ongoing immunosuppressant treatment; corticosteroid treatment exceeding 20 mg/day prednisone or equivalent within 7 days of the first dose of study drug infusion; 14. Known hypersensitivity or allergy to the active principle and/or formulations’ ingredients; history of severe allergy or anaphylaxis to murine or biologic agents; 15. Live or live attenuated vaccine within 28 days of first dose of study drug infusion; 16. History of significant cardiac or vascular disease including, but not limited to: history of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within 6 months before randomisation; congestive heart failure according to the New York Heart Association (NYHA) Functional Classification class III or IV; 17. History of drug abuse or alcohol abuse; 18. Unstable or uncontrolled medical or psychological condition; 19. Pregnant or breastfeeding female subject.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the ORR up to Week 28 of HLX01 versus Mabthera® in patients with low tumour burden, previously untreated Follicular Lymphoma (FL);Secondary Objective: - To obtain additional estimates of the efficacy of HLX01 and Mabthera® in patients with FL; - To compare the safety profile of HLX01 and Mabthera®; - To evaluate the immunogenicity of HLX01 and Mabthera®; - To measure the exposure to rituximab following HLX01 or Mabthera® treatment;Primary end point(s): ORR up to Week 28, defined as the proportion of patients achieving either complete response (CR) or partial response (PR) as best response from the first dose of study drug through Week 28 as assessed by a blinded independent review committee according to the Modified Lugano Response Classification 2014.;Timepoint(s) of evaluation of this end point: Week 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy: Time-to-progression of disease (TTPD), progression-free survival (PFS), and overall survival (OS), plus ORR at each assessable time point; - Safety and tolerability: Adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESI), laboratory abnormalities, physical examination, vital signs, and 12-lead electrocardiogram (ECG) - Immunogenicity: Anti-drug antibody (ADA) and neutralising antibody - Pharmacokinetics (PK): The maximum serum concentration (Cmax) and trough serum concentration (Ctrough) after each dose during induction period and selected doses thereafter - Pharmacodynamics: Depletion of B cell counts: absolute count and change from baseline;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Australia, Belgium, China, Czech Republic, France, Hungary, India, Italy, Poland, Romania, Russian Federation, Spain, Ukraine
Contacts
Public ContactGlobal Clinical Medical Affairs
Shanghai Henlius Biotech,Inc.
Outcome results
None listed