A Phase III Study to Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) with MabThera® in Subjects with Previously Untreated Follicular Lymphoma
- Conditions
- Follicular LymphomaMedDRA 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)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004223-36-ES
- Lead Sponsor
- Dr. Reddy’s Laboratories S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 284
1. Signed written informed consent.
2. Male or female subjects aged =18 years of age.
3. Histologically confirmed, Grade 1-3a, previously untreated, CD20-positive, LTB-FL as per Groupe D’Etude des Lymphomes Folliculaires (GELF) criteria. Subjects must have tissue available for the central pathology review, and a centrally-confirmed diagnosis prior to being randomised. Should a subject be eligible as per the central imaging review but not as per the Study Centre Review the subject will be considered eligible if confirmed both by the Investigator and the Medical Monitor. For any other disagreement in eligibility the subject will be considered ineligible.
4. Ann Arbor Stage II to IV of histological Grade 1, 2, or 3a.
5. ECOG status of 0 to 1.
6. Low tumour burden follicular lymphoma defined as:
· As per central radiological assessment, nodal or extranodal mass involvement with diameter measuring <7 cm
· As per central radiological assessment, involvement of <3 nodal sites with diameter measuring >3 cm
· Absence of systemic symptoms or B-symptoms* (asymptomatic)
*B-symptoms defined as weight loss >10% within last 6 months, recurrent or continuous night sweats, intermittent or continuous fever recorded as axillary or oral temperature >38°C for at least 3 days
· As per central radiological assessment, absence of splenomegaly (defined as spleen size higher than 16 cm by computed tomography [CT] scan)
· Absence of risk of vital organ compression based on clinical finding
· Absence of leukemic phase (leukemic phase defined as a count >5,000/µL of circulating tumour cells)
· Absence of clinically significant cytopenias (defined as a platelet count of <100,000/µL, haemoglobin <10 g/dL, or absolute neutrophil count <1,500/µL)
· Absence of clinically significant serous effusion based on clinical examination and CT scan
· Serum LDH not higher than the upper limit of normal (ULN) by local laboratory.
7. Subject has at least 1 measurable tumour mass in 2 dimensions as per central radiological assessment, 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.
8. Creatinine clearance =45 mL/min as calculated by the Cockcroft-Gault method.
9. Aspartate transaminase, alanine transaminase, alkaline phosphatase values =3 × ULN, total or conjugated bilirubin values =1.5 × ULN.
10. Life expectancy =3 months.
11. Able to comply with the study protocol.
12. If female subject, then subject should be non-pregnant, non-lactating. Adequate contraception or post-menopausal/non-childbearing status. Women of childbearing potential must practice effective birth control for the duration of the study and for 12 months after the last study drug dose. For this same duration, male subjects participating in the study should avoid passing the semen to female partners during sexual intercourse.
Are the trial subjects under 18? no
Number of subjects for this age rang
1. Prior use of rituximab or any CD20 monoclonal antibody for any reason.
2. Any contraindication to the use of rituximab.
3. Any prior therapy for follicular lymphoma (including but not limited to chemotherapy, radiotherapy).
4. Subjects who, in the opinion of the Investigator, require additional concomitant treatment for lymphoma.
5. Evidence of histologic transformation to high grade lymphoma or diffuse large B-cell lymphoma.
6. Known Central Nervous System (CNS) involvement by lymphoma. (Note: CNS imaging is not required unless clinically indicated).
7. Subjects on chronic supra-substitutive doses (defined as doses in excess of 7.5 mg per day of prednis one or prednis one equivalent for a period longer than 3 weeks) of systemic glucocorticoids.
8. Prior malignancy, other than non-melanoma skin cancer or intraepithelial cervical neoplasia, successfully treated more than 1 year before study inclusion.
9. Subjects with any of the following: known seropositivity for or history of active viral infection with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) positive or hepatitis B core antibody positive, hepatitis C virus (HCV) antibody positive.
10. Subjects with active tuberculosis (TB). Subjects with evidence of latent TB or a history of TB must have completed treatment or have initiated treatment for at least 1 month before the first dose of study drug (Day 1). Tuberculosis testing (QuantiFERON®-TB Gold-in-Tube test - QFT-GIT or QuantiFERON®-TB Gold Plus) is requested only if it is required by local regulations or practice.
11. Subjects who have received a live vaccine within last 3 months of the first administration of study drug.
12. Subjects with an active uncontrolled infection requiring systemic treatment at Screening or history of documented recurrent clinically significant infection within 6 months of study inclusion (e.g., 2 or more viral, bacterial or fungal infections requiring in-patient treatment).
13. Subjects with New York Heart Association (NYHA) class III or IV congestive heart failure or relevant arrhythmia or angina based on ECG with clinical judgment.
14. Subjects with known hypersensitivity to rituximab or its excipients, or to proteins of murine or other foreign origin.
15. History or presence of a medical condition or disease that in the Investigator's opinion would place the subject at an unacceptable risk for study participation.
16. Participation in any clinical study or having taken any investigational therapy during the 2-month period immediately preceding administration of the first dose of study drug.
17. Lactating or pregnant female.
18. Women of childbearing potential who do not consent to use highly effective methods of birth control (e.g., sterilisation, or other non-hormonal forms of contraception) during treatment and for at least 12 months after the last administration of study drug. True abstinence periodic abstinence (e.g., calendar ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
19. Subject has been previously enrolled and/or randomized in this study.
20. Subject likely not to be
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method