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

Dr. Reddy's Laboratories Limited317 enrolled

Overview

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

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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

317

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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) 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.. 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.

Outcomes

Primary Outcomes

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.

Time frame: Month 7 (Week 28)

Secondary Outcomes

Overall Response Rate (ORR)

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.

Time frame: Week 12, Week 28

Complete Response Rate

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.

Time frame: Week 28

Complete Response Rate as a Best Response

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.

Time frame: Week 28

Duration of Response (DOR)

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.

Time frame: Week 52

Progression-free Survival (PFS)

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.

Time frame: Week 52

Overall Survival (OS)

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.

Time frame: Week 52

Number of Participants With Adverse Events

The safety and tolerability of DRL\_RI and MabThera® in participants with CD20-positive, LTB-FL was evaluated.

Time frame: From Screening (Day -28 to -1) up to 52 weeks

Number of Participants With Positive Anti-drug Antibody (ADA)

The immunogenicity of the Proposed Rituximab Biosimilar (DRL\_RI) with MabThera® among trial participants was compared.

Time frame: On Day 1, Week 2, Week 3, Week 4, Week 12 post dose

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

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes