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Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma (FLINTER)

NCT03976102

Description:

The primary objective of the current study is to demonstrate the equivalent efficacy of rituximab (DRL_RI) and MabThera® in subjects with Low Tumor Burden Follicular Lymphoma (LTB-FL). Also evaluated by Pharmacokinetic, safety, and immunogenicity assessment between a proposed biosimilar (DRL_RI) and the RMP, as an component of clinical study program, and collectively providing the evidence of biosimilarity. The study will compare the safety and efficacy of DRL_RI vs MabThera in patients with Low Tumor Burden Follicular Lymphoma (LTB-FL). The primary objective is to establish comparative efficacy as measured by ORR at week 28

Related Conditions:
  • Follicular Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma (FLINTER)
  • Official Title: A Double-blind, Parallel-group, Phase III Study to Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in Subjects With Previously Untreated (CD)20-Positive LTB Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: RI-01-006
  • NCT ID: NCT03976102

Conditions

  • Follicular Lymphoma

Interventions

DrugSynonymsArms
DRL_RI (Proposed rituximab biosimilar)Arm A: DRL_RI

Purpose

The primary objective of the current study is to demonstrate the equivalent efficacy of rituximab (DRL_RI) and MabThera® in subjects with Low Tumor Burden Follicular Lymphoma (LTB-FL). Also evaluated by Pharmacokinetic, safety, and immunogenicity assessment between a proposed biosimilar (DRL_RI) and the RMP, as an component of clinical study program, and collectively providing the evidence of biosimilarity. The study will compare the safety and efficacy of DRL_RI vs MabThera in patients with Low Tumor Burden Follicular Lymphoma (LTB-FL). The primary objective is to establish comparative efficacy as measured by ORR at week 28

Detailed Description

      It is planned to randomise approx. 284 subjects at approximately 130 study sites worldwide.
      Subjects with LTB-FL will be randomized to receive either DRL_RI or MabThera®.

      The study specific objectives are mentioned below:

      Primary Objective:

        -  To demonstrate the equivalent efficacy of DRL_RI (biosimilar rituximab) and MabThera in
           subjects with CD20-positive, LTB FL, as measured by overall response rate (ORR) at Week
           28 Secondary Objectives:

        -  To compare the progression-free survival (PFS), overall survival (OS), and duration of
           response (DOR) of DRL_RI with MabThera in subjects with CD20-positive, LTB FL.

        -  To compare the safety, tolerability, and immunogenicity of DRL_RI with MabThera in
           subjects with CD20-positive, LTB-FL.

      Exploratory Objectives

        -  To explore the pharmacokinetic (PK) parameters of DRL_RI and MabThera, using a
           population-PK modelling approach.

        -  To explore the pharmacodynamic parameters of DRL_RI and MabThera.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: DRL_RIExperimentalDRL_RI (rituximab-Dr. Reddy's Lab) for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Weeks 12, 20, 28 and 36
  • DRL_RI (Proposed rituximab biosimilar)
Arm B: MabThera®Active ComparatorMabThera® for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Week 12, 20, 28 and 36.

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Subject is Male or female subjects aged ≥18 years of age.
    
              2. Subject is histologically confirmed, Grade 1-3a, previous ly untreated, CD20-pos
                 itive.
    
              3. Subject has Ann Arbor Stage II to IV and ECOG status of 0 to 1.
    
              4. Subject has Low tumor burden follicular lymphoma as per Groupe d'Etude des Lymphomes
                 Folliculaires (GELF) Criteria
    
              5. Subject has at least 1 measurable tumor mass in 2 dimensions, and the mass must be:
    
                   1. Nodal lesion >15 mm in the longest dimension; or
    
                   2. Noda l lesion >10 mm to he longest dimension; dimens ion and >10 mm in the
                      shortest dimension; or
    
                   3. Extra-nodal lesion with both long and short dimensions ≥10 mm.
    
              6. Subject has Life expectancy ≥3 months.
    
              7. If female subject, then subject should be non-pregnant, non-lactating.
    
            Exclusion Criteria:
    
              1. Subject with prior use of rituximab or any CD20 monoclonal antibody for any reason.
    
              2. Subjects with known hypersensitivity to rituximab or its excipients, or to proteins of
                 murine or other foreign origin.
    
              3. Any prior therapy for follicular lymphoma (including but not limited to chemotherapy,
                 radiotherapy) or subjects on chronic supra-substitutive doses of systemic
                 gluco-corticosteriods.
    
              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. Subjects with known sero-positivity 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.
    
              7. Subjects who have received a live vaccine within last 3 months of the first
                 administration of study drug.
    
              8. Subjects with 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.
    
              9. Participation in any clinical study or having taken any investigational therapy
                 (within 2-months of the first dose of study drug.
    
             10. Women of childbearing potential who do not consent to use highly effective methods of
                 birth control.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Response Rate (ORR) measured for follicular lymphoma
    Time Frame:Month 7 (Week 28)
    Safety Issue:
    Description:The primary endpoint is ORR, defined as the proportion of subjects in each treatment group that achieve complete response (CR), unconfirmed complete response (CRu) or partial response (PR) at Month 7 (Week 28) with the response criteria for malignant lymphoma

    Secondary Outcome Measures

    Measure:Progression-free survival
    Time Frame:52 Weeks
    Safety Issue:
    Description:Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
    Measure:Overall response rate
    Time Frame:12 Weeks
    Safety Issue:
    Description:Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
    Measure:Overall survival
    Time Frame:52 Weeks/End of Study
    Safety Issue:
    Description:Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
    Measure:Duration of response
    Time Frame:52 Weeks/End of Study
    Safety Issue:
    Description:Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
    Measure:Safety in terms of Adverse Events
    Time Frame:52 Weeks
    Safety Issue:
    Description:Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL in terms of Adverse events (AEs) as assessed by the NCI CTCAE version 5.0.
    Measure:Tolerability in terms of Adverse Events
    Time Frame:52 Weeks
    Safety Issue:
    Description:Compared between DRL_RI with MabThera® for subjects with severity (Grade 3 or Higher) of Treatment Emergent Adverse Events, as assessed by the NCI CTCAE v5.0.
    Measure:Analysis of BAb and NAb in Blood
    Time Frame:52 Weeks
    Safety Issue:
    Description:Immunogenicity compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL in terms of Anti-DRL_RI antibodies

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Dr. Reddy's Laboratories Limited

    Trial Keywords

    • Follicular Lymphoma
    • Dr. Reddy's Rituximab
    • Biosimiliar (DRL_RI)
    • FLINTER

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