To Compare Efficacy and Safety Between CT-P10 and Rituxan in Patients With Low Tumour Burden Follicular Lymphoma

Study Overview
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Brief Summary
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To demonstrate that CT-P10 is similar to Rituxan in terms of efficacy as determined by overall response rate at 7 months

Official Title
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A Phase 3, Randomised, Parallel-group, Active-controlled, Double-blind Study to Compare Efficacy and Safety Between CT-P10 and Rituxan in Patients With Low Tumour Burden Follicular Lymphoma

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Biological: CT-P10
* Biological: Rituxan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of low tumour burden, CD20+ follicular lymphoma Ann Arbor Stage II, III or IV Exclusion Criteria: Has receive rituximab Allergies or hypersensitivity to murine, chimeric, human or humanised proteins Previous treatment for NHL Any malignancy Current or recent treatment with any other investigational medicinal product or device pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CT-P10<br>CT-P10, intervention 375mg/m2, intravenous, 4 cycles in induction period and additional 12 cycles in maintenance period | Biological: CT-P10<br>* 375mg/m2, IV on day1 of 4 cycles in induction period, and 12 cycles in maintenance period.<br>|
| Active Comparator: Rituxan<br>Rituxan, 375mg/m2 intravenous, 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period. | Biological: Rituxan<br>* 375mg/m2, IV on day1 of 4 cycles in induction period, Rituxan for the first 6 cycles and CT-P10 for the last 6 cycles in maintenance period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint - Overall Response Rate by 7 Months | ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: >75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression. | During the Month 7 (up to Maintenance Cycle 3; Week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Endpoint - ORR Over the Study Period | ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed CR (CRu), or partial response (PR). Per 1999 IWG criteria, the disease status was assessed by using contrasted CT and/or MRI, and CR, CRu, and PR were defined as followings; CR=Disappearance of all clinical/radiographic evidence of disease: regression of lymph nodes to normal size, absence of B-symptoms, bone marrow involvement, and organomegaly, and normal LDH level; CRu=Regression of measurable disease: >75% decrease in SPD of target lesions and in each target lesions. no increase in the size of non-target lesions, neither new lesion nor organomegaly measured; PR=Regression of measurable disease: ≥50% decrease in SPD of target lesions and no evidence of disease progression. | up to 27 months | 
| Secondary PD Endpoint - B-cell Kinetics (B-cell Depletion and Recovery) | B-cell kinetics were demonstrated by median values of B-cell counts. Any values below the LLoQ were set as LLoQ which was 20 cells/μL. | Baseline, Induction Cycle 1 (predose, 1 hr postdose), Induction Cycle 2 to 4 (predose), EOT1/EOT2 (anytime), Maintenance Cycle 1 to 2 (predose, 1hr postdose) and Maintenance Cycle 3 (predose). | 
| Secondary PK Endpoints - Cmax |  | 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose) | 
| Secondary PK Endpoints - Ctrough |  | 1, 2, 3, 4, 12, 20 weeks (predose, 1 hr post dose), EOT1/EOT2 (anytime during the day) and 28 week (predose) | 
| Secondary Efficacy Endpoint - Progression-free Survival (PFS) | PFS was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death from any cause, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses. | Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter). | 
| Secondary Efficacy Endpoint - Overall Survival (OS) | Overall survival was defined as the interval between randomization and death from any cause. Locally reviewed data was used for the secondary efficacy analyses. | Overall study period (median follow-up of 29.2 months) | 
| Secondary Efficacy Endpoint - Time-to Progression (TTP) | Time to progression was defined as the interval between randomization and disease progression/relapse by IWG 1999 (at least a 50% increase of any single nodal after smallest decrease) or death as a result of lymphoma, whichever occurred first. Locally reviewed data was used for the secondary efficacy analyses. | Overall study period (Baseline, Month 3, 7, 13, 19 27, and every 6 months thereafter). |