FLINTER: Compare Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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:
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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.
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To compare the safety, tolerability, and immunogenicity of DRL_RI with MabThera in subjects with CD20-positive, LTB-FL.
Exploratory Objectives
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To explore the pharmacokinetic (PK) parameters of DRL_RI and MabThera, using a population-PK modelling approach.
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To explore the pharmacodynamic parameters of DRL_RI and MabThera.
Study Design
Arms and Interventions
| 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 |
Biological: DRL_RI (Proposed rituximab biosimilar)
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. |
Other: MabThera®
Reference product rituximab, 100mg and 500mg, concentrate for solution for infusion
|
Outcome Measures
Primary Outcome Measures
- Best Overall Response Rate (BORR) measured for low tumor burden follicular lymphoma, up to week 28 [BORR up to Month 7 (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 [Upto week 52]
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
- Overall response rate (ORR) at Week 12, 28 & 52 [at week 12, week 28 and week 52]
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
- Overall survival up to 52 weeks/End of Study (EOS) [upto week 52]
Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL
- Duration of response (DOR) up to 52 weeks/EOS [upto week 52]
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) [upto week 52]
The liver enzyme levels will be compared between the groups.
- The safety and tolerability in terms of serum SGPT (U/L) [upto week 52]
The liver enzyme levels will be compared between the groups
- Safety and tolerability in terms of serum creatinine levels (µmol/L) [upto week 52]
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. [upto week 52]
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 [upto week 52]
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. [upto week 52]
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) [upto week 52]
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 [upto week 52]
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 [upto week 52]
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 [upto week 52]
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. [upto week 52]
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 [upto week 52]
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 [upto week 52]
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 [upto week 52]
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)
Other Outcome Measures
- Exploratory-To compare ORR evaluated in accordance with the Lugano criteria [upto week 52]
Overall response rate based on the Lugano criteria 14 for those subjects with available positron emission tomography (PET) data
- Exploratory- to explore the PK parameters of DRL_RI and MabThera®, using a population-PK modelling approach [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.
- Exploratory- to explore the pharmacodynamic parameters of DRL_RI and MabThera [upto week 52]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject is Male or female subjects aged ≥18 years of age.
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Subject is histologically confirmed, Grade 1-3a, previous ly untreated, CD20-pos itive.
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Subject has Ann Arbor Stage II to IV and ECOG status of 0 to 1.
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Subject has Low tumor burden follicular lymphoma as per Groupe d'Etude des Lymphomes Folliculaires (GELF) Criteria
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Subject has at least 1 measurable tumor mass in 2 dimensions, and the mass must be:
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Nodal lesion >15 mm in the longest dimension; or
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Noda l lesion >10 mm to he longest dimension; dimens ion and >10 mm in the shortest dimension; or
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Extra-nodal lesion with both long and short dimensions ≥10 mm.
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Subject has Life expectancy ≥3 months.
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If female subject, then subject should be non-pregnant, non-lactating.
Exclusion Criteria:
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Subject with prior use of rituximab or any CD20 monoclonal antibody for any reason.
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Subjects with known hypersensitivity to rituximab or its excipients, or to proteins of murine or other foreign origin.
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Any prior therapy for follicular lymphoma (including but not limited to chemotherapy, radiotherapy) or subjects on chronic supra-substitutive doses of systemic gluco-corticosteriods.
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Subjects who, in the opinion of the Investigator, require additional concomitant treatment for lymphoma.
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Evidence of histologic transformation to high grade lymphoma or diffuse large B-cell lymphoma.
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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..
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Subjects who have received a live vaccine within last 3 months of the first administration of study drug.
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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.
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Participation in any clinical study or having taken any investigational therapy (within 2-months of the first dose of study drug.
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Women of childbearing potential who do not consent to use highly effective methods of birth control.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Oncology Institute of Hope and Innovation | Whittier | California | United States | 90602 |
| 2 | American Oncology Partners of Maryland | Bethesda | Maryland | United States | 20817 |
| 3 | University of Tennessee Medical Center - Cancer Institute | Knoxville | Tennessee | United States | 37920 |
| 4 | Gulf coast Oncology Associates, PA | Houston | Texas | United States | 77089 |
Sponsors and Collaborators
- Dr. Reddy's Laboratories Limited
- Parexel
Investigators
- Study Director: Eliso Sopia, MD, Parexel
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RI-01-006