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

NCT03976102 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: RI-01-006
• Study Type: interventional
• Target: 317
• Locations: 1 country
• Sites: 4

Brief Summary

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 up to week 28

Conditions

Follicular Lymphoma

Keywords

Follicular Lymphoma; Dr. Reddy's Rituximab; Biosimilar (DRL_RI); FLINTER

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (BORR) for Low Tumor Burden Follicular Lymphoma

  Best Overall Response Rate (BORR) is defined as the proportion of participants in each treatment group that achieved a best overall response of either Complete response (CR), unconfirmed Complete response (CRu) or Partial response (PR), up to Month 7 (Week 28) based on central radiology review in accordance with the Cheson, 1999 response criteria for Non-Hodgkin's Lymphomas. As per Cheson 1999, response criteria for target lesions and assessed by radiology: Complete response (CR): All lesions with a longest diameter should be regressed to normal size (≤ 15 mm) or short axis regressed to ≤ 10 mm with confirmed Bone marrow normalization; unconfirmed Complete response (CRu): All lesions with a longest diameter should be regressed to normal size (≤ 15 mm) or short axis regressed to ≤ 10 mm with non-confirmed Bone marrow normalization; Partial Response (PR): ≥ 50 % decrease of sum of products of diameter(SPD) of all the target lesions; Overall Response (OR)=CR+CRu+PR.

  Month 7 (Week 28)

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  Week 12, Week 28

• Complete Response Rate

  Week 28

• Complete Response Rate as a Best Response

  Week 28

• Duration of Response (DOR)

  Week 52

• Progression-free Survival (PFS)

  Week 52

Study Arms (2)

Arm A: DRL_RI

EXPERIMENTAL

DRL\_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

Biological: DRL_RI (Proposed rituximab biosimilar)

Arm B: MabThera®

ACTIVE COMPARATOR

MabThera® for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Week 12, 20, 28 and 36.

Other: MabThera®

Interventions

DRL_RI (Proposed rituximab biosimilar) BIOLOGICAL

Proposed rituximab biosimilar, 100mg and 500mg, concentrate for solution for infusion

Arm A: DRL_RI

MabThera® OTHER

Reference product rituximab, 100mg and 500mg, concentrate for solution for infusion

Arm B: MabThera®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is Male or female subjects aged ≥18 years of age.
• Subject is histologically confirmed, Grade 1-3a, previous ly untreated, CD20-pos itive.
• Subject has Ann Arbor Stage II to IV and ECOG status of 0 to 1.
• Subject has Low tumor burden follicular lymphoma as per Groupe d'Etude des Lymphomes Folliculaires (GELF) Criteria
• Subject has at least 1 measurable tumor mass in 2 dimensions, and the mass must be:
• Nodal lesion \>15 mm in the longest dimension; or
• Noda l lesion \>10 mm to he longest dimension; dimens ion and \>10 mm in the shortest dimension; or
• Extra-nodal lesion with both long and short dimensions ≥10 mm.
• Subject has Life expectancy ≥3 months.
• If female subject, then subject should be non-pregnant, non-lactating.

You may not qualify if:

• Subject with prior use of rituximab or any CD20 monoclonal antibody for any reason.
• Subjects with known hypersensitivity to rituximab or its excipients, or to proteins of murine or other foreign origin.
• Any prior therapy for follicular lymphoma (including but not limited to chemotherapy, radiotherapy) or subjects on chronic supra-substitutive doses of systemic gluco-corticosteriods.
• Subjects who, in the opinion of the Investigator, require additional concomitant treatment for lymphoma.
• Evidence of histologic transformation to high grade lymphoma or diffuse large B-cell lymphoma.
• Subjects with known sero-positivity for or history of active viral infection with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) will be excluded. And if positive for hepatitis B core antibody or hepatitis C virus (HCV) antibody can only be enrolled if HBV - DNA level \<20 IU/mL (or 112 copies/mL) and HCV - RNA is negative respectively by PCR test..
• Subjects who have received a live vaccine within last 3 months of the first administration of study drug.
• 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.
• Participation in any clinical study or having taken any investigational therapy (within 2-months of the first dose of study drug.
• Women of childbearing potential who do not consent to use highly effective methods of birth control.

Sponsors & Collaborators

• Dr. Reddy's Laboratories Limited: lead
• Parexel: collaborator

Study Sites (4)

The Oncology Institute of Hope and Innovation

Whittier, California, 90602, United States

Location

American Oncology Partners of Maryland

Bethesda, Maryland, 20817, United States

Location

University of Tennessee Medical Center - Cancer Institute

Knoxville, Tennessee, 37920, United States

Location

Gulf coast Oncology Associates, PA

Houston, Texas, 77089, United States

Location

Related Publications (1)

• Maharaj N, Uppada DR, Eswaraiah A, Kakkattu R, Reddy P, Kalenik VA, Belada D, Ramos AO, Kim JS, Baranau YV. Efficacy and safety of rituximab biosimilar (DRL_RI) versus MabThera(R) in low-tumor-burden follicular lymphoma: the FLINTER study. Ther Adv Med Oncol. 2025 May 24;17:17588359251339925. doi: 10.1177/17588359251339925. eCollection 2025.

  PMID: 40421128 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Head - Clinical Development
• Organization: Dr. Reddy's Laboratories Ltd.

RI-01-006@drreddys.com

91-40-4464-4000

Study Officials

• Eliso Sopia, MD

  Parexel

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Clinical Phase III, randomised, multicentre, double-blind study to demonstrate the equivalence of DRL\_RI to MabThera® in subjects with previously untreated, LTB-FL.

Study Record Dates

• First Submitted: April 15, 2019
• First Posted: June 5, 2019
• Study Start: May 15, 2019
• Primary Completion: September 28, 2022
• Study Completion: February 27, 2023
• Last Updated: January 22, 2024
• Results First Posted: January 22, 2024

Record last verified: 2024-01

Locations

US (4)