- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03976102
Compare Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma (FLINTER)
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
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
It is planned to randomise approx. 312 subjects at approximately ≥ 130 study sites worldwide. Subjects with LTB-FL will be randomized to receive either DRL_RI or MabThera®. Till date, 68 patients have been randomized for the study.
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) up to Week 28 evaluated in accordance with Cheson, 1999 response criteria for Non-Hodgkin's Lymphomas.
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
California
-
Whittier, California, United States, 90602
- The Oncology Institute of Hope and Innovation
-
-
Maryland
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Bethesda, Maryland, United States, 20817
- American Oncology Partners of Maryland
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-
Tennessee
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Knoxville, Tennessee, United States, 37920
- University of Tennessee Medical Center - Cancer Institute
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-
Texas
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Houston, Texas, United States, 77089
- Gulf coast Oncology Associates, PA
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A: DRL_RI
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
|
Proposed rituximab biosimilar, 100mg and 500mg, concentrate for solution for infusion
|
Active Comparator: Arm B: MabThera®
MabThera® for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Week 12, 20, 28 and 36.
|
Reference product rituximab, 100mg and 500mg, concentrate for solution for infusion
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best Overall Response Rate (BORR) for Low Tumor Burden Follicular Lymphoma
Time Frame: Month 7 (Week 28)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Week 12, Week 28
|
The overall response rate (ORR) is defined as proportion of participants in each treatment group achieved a complete response or partial response at week 12 and week 28 based on central radiology review in accordance with published response criteria for malignant lymphoma.
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 (uCR): 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+uCR+PR.
|
Week 12, Week 28
|
Complete Response Rate
Time Frame: Week 28
|
Complete Response rate is defined as the proportion of participants in each treatment group who achieved complete response up to particular visit based on investigator assessment in accordance with the response criteria for malignant lymphoma.
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.
|
Week 28
|
Complete Response Rate as a Best Response
Time Frame: Week 28
|
Complete Response Rate as a Best Response is defined as the proportion of participants in each treatment group that achieved the best complete response up to Week 28 based on central radiology review in accordance with the Cheson 1999, response criteria for malignant lymphoma.
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.
|
Week 28
|
Duration of Response (DOR)
Time Frame: Week 52
|
Duration of response (DOR) defined as the time from date of the first documentation of tumor response (Complete Response, unconfirmed complete response or partial response) to the date of first documentation of progressive disease (PD) or to death due to any cause up to 52 weeks/ End of study (EOS). Progression is defined as per Cheson 1999, response criteria is: Target Nodal SPD Progression: at least one node must be abnormal, and the SPD of all nodes must increase by ≥ 50% from its nadir SPD. Target Extranodal SPD Progression: at least one extranodal lesion must be present and the SPD of all extranodal lesions must increase by ≥ 50% from its nadir SPD. Also, if a patient had any unequivocal progression in non-target lesions; and detection of any new nodal lesion (longest diameter [LDi] 15mm with an absolute increase of 5mm) his/her response was considered as Progressive disease. |
Week 52
|
Progression-free Survival (PFS)
Time Frame: Week 52
|
Progression-free survival (PFS) is defined as the time from date of randomization to the date of documented progressive disease or death due to any cause. Progression is defined as per Cheson 1999, response criteria is: Target Nodal SPD Progression: at least one node must be abnormal, and the SPD of all nodes must increase by ≥ 50% from its nadir SPD. Target Extranodal SPD Progression: at least one extranodal lesion must be present and the SPD of all extranodal lesions must increase by ≥ 50% from its nadir SPD. Also, if a patient had any unequivocal progression in non-target lesions; and detection of any new nodal lesion (LDi 15mm with an absolute increase of 5mm) his/her response was considered as Progressive disease. |
Week 52
|
Overall Survival (OS)
Time Frame: Week 52
|
The Overall survival (OS) defined as the time from date of randomization to the date of death from any cause up to 52 weeks or EOS.
|
Week 52
|
Number of Participants With Adverse Events
Time Frame: From Screening (Day -28 to -1) up to 52 weeks
|
The safety and tolerability of DRL_RI and MabThera® in participants with CD20-positive, LTB-FL was evaluated.
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From Screening (Day -28 to -1) up to 52 weeks
|
Number of Participants With Positive Anti-drug Antibody (ADA)
Time Frame: On Day 1, Week 2, Week 3, Week 4, Week 12 post dose
|
The immunogenicity of the Proposed Rituximab Biosimilar (DRL_RI) with MabThera® among trial participants was compared.
|
On Day 1, Week 2, Week 3, Week 4, Week 12 post dose
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory-To compare ORR evaluated in accordance with the Lugano criteria
Time Frame: upto week 52
|
Overall response rate based on the Lugano criteria 14 for those subjects with available positron emission tomography (PET) data
|
upto week 52
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Exploratory- to explore the PK parameters of DRL_RI and MabThera®, using a population-PK modelling approach
Time Frame: upto week 52
|
• Plasma concentrations of rituximab will be compared and summarized for the PK Sub-population by treatment group and visit at which samples were taken.
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upto week 52
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Exploratory- to explore the pharmacodynamic parameters of DRL_RI and MabThera
Time Frame: upto week 52
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Potential differences in pharmacodynamic parameters (e.g., area under the effect curve [AUEC] of circulating B-cells depletion) for DRL_RI and MabThera® will be investigated
|
upto week 52
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Eliso Sopia, MD, Parexel
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, Follicular
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- RI-01-006
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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