Back to resultsCompare Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma (FLINTER)
Primary Purpose
Follicular Lymphoma
Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
DRL_RI (Proposed rituximab biosimilar)
MabThera®
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma focused on measuring Follicular Lymphoma, Dr. Reddy's Rituximab, Biosimiliar (DRL_RI), FLINTER
Eligibility Criteria
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.
Sites / Locations
- The Oncology Institute of Hope and Innovation
- American Oncology Partners of Maryland
- University of Tennessee Medical Center - Cancer Institute
- Gulf coast Oncology Associates, PA
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A: DRL_RI
Arm B: MabThera®
Arm Description
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
MabThera® for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Week 12, 20, 28 and 36.
Outcomes
Primary Outcome Measures
Best Overall Response Rate (BORR) measured for low tumor burden follicular lymphoma, up to week 28
Primary endpoint: The primary endpoint is Best Overall Response Rate (BORR), up to Month 7 (Week 28) based on central radiology review in accordance with the Cheson, 1999 response criteria for Non-Hodgkin's Lymphomas.
Secondary Outcome Measures
Progression-free survival
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
Overall response rate (ORR) at Week 12, 28 & 52
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
Overall survival up to 52 weeks/End of Study (EOS)
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
Duration of response (DOR) up to 52 weeks/EOS
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
The safety and tolerability in terms of serum SGOT levels (U/L)
The liver enzyme levels will be compared between the groups.
The safety and tolerability in terms of serum SGPT (U/L)
The liver enzyme levels will be compared between the groups
Safety and tolerability in terms of serum creatinine levels (µmol/L)
serum creatinine levels will be compared between the groups at all scheduled visits
The safety and tolerability in terms of incidence of adverse events reported. As described below the data will be compared between the groups.
The incidence of infusion related reactions (number of subjects reported the event) and all other Treatment-Emergent Adverse Events reported in the trial (number of subjects reported the event and number of events reported for each type of adverse event)
The safety and tolerability in terms of Blood Pressure (mm of hg) will be compared between the groups
The change of BP (mm of hg) from baseline to scheduled visits by treatment group
The safety and tolerability in terms of ECG parameters. As described below the data will be compared between the groups.
Summary of subjects with designated changes in VR (beats/minute) and QT, QTcF, PR, QRS and RR intervals (milli seconds) of ECG from baseline to EOS by treatment group
The safety and tolerability in terms of absolute Neutrophil count (total count/L)
absolute Neutrophil count will be compared between the groups at all scheduled visits
The safety and tolerability in terms of Respiratory rate (breaths/minute) will be compared between the groups
The change of Respiratory rate (breaths/minute) from baseline to scheduled visits by treatment group
The safety and tolerability in terms of Heart rate (beats/minute) will be compared between the groups
The change of Heart rate (beats/minute) from baseline to scheduled visits by treatment group
The safety and tolerability in terms of temperature (°C) will be compared between the groups
The change of temperature (°C) from baseline to scheduled visits by treatment group
The safety and tolerability in terms of ECOG change. As described below the data will be compared between the groups.
Summary of ECOG performance status (on a scale of grade 0 to 5) at scheduled visits by treatment group.
to compare immunogenicity in terms of incidence of anti-drug antibodies
The immunogenicity of the Proposed Rituximab Biosimilar (DRL_RI) with MabThera® among trial subjects will be compared as mentioned below:
• Comparison of incidence of subjects developing anti-drug antibodies (in number of individuals)
to compare immunogenicity in terms of incidence of titres
The immunogenicity of the Proposed Rituximab Biosimilar (DRL_RI) with MabThera® among trial subjects will be compared as mentioned below:
• For those positive for anti-drug antibodies their titres will be compared (in dilutions i.e. 1/10, 1/100)
to compare immunogenicity in terms of incidence of neutralizing antibodies
The immunogenicity of the Proposed Rituximab Biosimilar (DRL_RI) with MabThera® among trial subjects will be compared as mentioned below:
• incidence of subjects positive for neutralizing antibodies will be compared (in number of individuals)
Full Information
NCT ID
NCT03976102
First Posted
April 15, 2019
Last Updated
May 27, 2022
Sponsor
Dr. Reddy's Laboratories Limited
Collaborators
Parexel
1. Study Identification
Unique Protocol Identification Number
NCT03976102
Brief Title
Compare Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 1, 2019 (Actual)
Primary Completion Date
September 30, 2022 (Anticipated)
Study Completion Date
March 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dr. Reddy's Laboratories Limited
Collaborators
Parexel
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma
Keywords
Follicular Lymphoma, Dr. Reddy's Rituximab, Biosimiliar (DRL_RI), FLINTER
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Clinical Phase III, randomised, multicentre, double-blind study to demonstrate the equivalence of DRL_RI to MabThera® in subjects with previously untreated, LTB-FL.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
317 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: DRL_RI
Arm Type
Experimental
Arm Description
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
Arm Title
Arm B: MabThera®
Arm Type
Active Comparator
Arm Description
MabThera® for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Week 12, 20, 28 and 36.
Intervention Type
Biological
Intervention Name(s)
DRL_RI (Proposed rituximab biosimilar)
Intervention Description
Proposed rituximab biosimilar, 100mg and 500mg, concentrate for solution for infusion
Intervention Type
Other
Intervention Name(s)
MabThera®
Intervention Description
Reference product rituximab, 100mg and 500mg, concentrate for solution for infusion
Primary Outcome Measure Information:
Title
Best Overall Response Rate (BORR) measured for low tumor burden follicular lymphoma, up to week 28
Description
Primary endpoint: The primary endpoint is Best Overall Response Rate (BORR), up to Month 7 (Week 28) based on central radiology review in accordance with the Cheson, 1999 response criteria for Non-Hodgkin's Lymphomas.
Time Frame
BORR up to Month 7 (Week 28)}
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
Time Frame
Upto week 52
Title
Overall response rate (ORR) at Week 12, 28 & 52
Description
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
Time Frame
at week 12, week 28 and week 52
Title
Overall survival up to 52 weeks/End of Study (EOS)
Description
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
Time Frame
upto week 52
Title
Duration of response (DOR) up to 52 weeks/EOS
Description
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
Time Frame
upto week 52
Title
The safety and tolerability in terms of serum SGOT levels (U/L)
Description
The liver enzyme levels will be compared between the groups.
Time Frame
upto week 52
Title
The safety and tolerability in terms of serum SGPT (U/L)
Description
The liver enzyme levels will be compared between the groups
Time Frame
upto week 52
Title
Safety and tolerability in terms of serum creatinine levels (µmol/L)
Description
serum creatinine levels will be compared between the groups at all scheduled visits
Time Frame
upto week 52
Title
The safety and tolerability in terms of incidence of adverse events reported. As described below the data will be compared between the groups.
Description
The incidence of infusion related reactions (number of subjects reported the event) and all other Treatment-Emergent Adverse Events reported in the trial (number of subjects reported the event and number of events reported for each type of adverse event)
Time Frame
upto week 52
Title
The safety and tolerability in terms of Blood Pressure (mm of hg) will be compared between the groups
Description
The change of BP (mm of hg) from baseline to scheduled visits by treatment group
Time Frame
upto week 52
Title
The safety and tolerability in terms of ECG parameters. As described below the data will be compared between the groups.
Description
Summary of subjects with designated changes in VR (beats/minute) and QT, QTcF, PR, QRS and RR intervals (milli seconds) of ECG from baseline to EOS by treatment group
Time Frame
upto week 52
Title
The safety and tolerability in terms of absolute Neutrophil count (total count/L)
Description
absolute Neutrophil count will be compared between the groups at all scheduled visits
Time Frame
upto week 52
Title
The safety and tolerability in terms of Respiratory rate (breaths/minute) will be compared between the groups
Description
The change of Respiratory rate (breaths/minute) from baseline to scheduled visits by treatment group
Time Frame
upto week 52
Title
The safety and tolerability in terms of Heart rate (beats/minute) will be compared between the groups
Description
The change of Heart rate (beats/minute) from baseline to scheduled visits by treatment group
Time Frame
upto week 52
Title
The safety and tolerability in terms of temperature (°C) will be compared between the groups
Description
The change of temperature (°C) from baseline to scheduled visits by treatment group
Time Frame
upto week 52
Title
The safety and tolerability in terms of ECOG change. As described below the data will be compared between the groups.
Description
Summary of ECOG performance status (on a scale of grade 0 to 5) at scheduled visits by treatment group.
Time Frame
upto week 52
Title
to compare immunogenicity in terms of incidence of anti-drug antibodies
Description
The immunogenicity of the Proposed Rituximab Biosimilar (DRL_RI) with MabThera® among trial subjects will be compared as mentioned below:
• Comparison of incidence of subjects developing anti-drug antibodies (in number of individuals)
Time Frame
upto week 52
Title
to compare immunogenicity in terms of incidence of titres
Description
The immunogenicity of the Proposed Rituximab Biosimilar (DRL_RI) with MabThera® among trial subjects will be compared as mentioned below:
• For those positive for anti-drug antibodies their titres will be compared (in dilutions i.e. 1/10, 1/100)
Time Frame
upto week 52
Title
to compare immunogenicity in terms of incidence of neutralizing antibodies
Description
The immunogenicity of the Proposed Rituximab Biosimilar (DRL_RI) with MabThera® among trial subjects will be compared as mentioned below:
• incidence of subjects positive for neutralizing antibodies will be compared (in number of individuals)
Time Frame
upto week 52
Other Pre-specified Outcome Measures:
Title
Exploratory-To compare ORR evaluated in accordance with the Lugano criteria
Description
Overall response rate based on the Lugano criteria 14 for those subjects with available positron emission tomography (PET) data
Time Frame
upto week 52
Title
Exploratory- to explore the PK parameters of DRL_RI and MabThera®, using a population-PK modelling approach
Description
• Plasma concentrations of rituximab will be compared and summarized for the PK Sub-population by treatment group and visit at which samples were taken.
Time Frame
upto week 52
Title
Exploratory- to explore the pharmacodynamic parameters of DRL_RI and MabThera
Description
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
Time Frame
upto week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eliso Sopia, MD
Organizational Affiliation
Parexel
Official's Role
Study Director
Facility Information:
Facility Name
The Oncology Institute of Hope and Innovation
City
Whittier
State/Province
California
ZIP/Postal Code
90602
Country
United States
Facility Name
American Oncology Partners of Maryland
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
University of Tennessee Medical Center - Cancer Institute
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States
Facility Name
Gulf coast Oncology Associates, PA
City
Houston
State/Province
Texas
ZIP/Postal Code
77089
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Compare Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma
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