To Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan

Study Overview
=================
Brief Summary
-----------------
This study is a Phase 3 prospective, randomised, parallel-group, active controlled, double blind, multicentre, international study with 2 coprimary endpoints designed to demonstrate equivalence in pharmacokinetics (Part 1), as well as noninferiority in efficacy (Part 2), of CT-P10 to Rituxan when coadministered with CVP and to assess efficacy and safety in patients with advanced (stage III-IV) FL. Part 1 and Part 2 of the study will run in parallel.

Official Title
-----------------
A Phase 3, Randomised, Parallel-Group, Active-Controlled, Double-Blind Study to Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan, Each Administered in Combination With Cyclophosphamide, Vincristine, and Prednisone (CVP) in Patients With Advanced Follicular Lymphoma

Conditions
-----------------
Lymphoma, Follicular

Intervention / Treatment
-----------------
* Biological: Rituxan
* Biological: CT-P10
* Drug: Cyclophosphamide
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient is male or female older than 18 years. Patient has histologically confirmed FL according to the World Health Organization 2008 classification (Jaffe 2009); grades 1 to 3a based on local laboratory review. Patient has at least 1 measurable tumour mass that has not previously been irradiated, and the mass must be: greater than 1.5 cm in the longest dimension or between 1.1 and 1.5 cm in the longest dimension and greater than 1.0 cm in the shortest axis Patient has confirmed CD20+ lymphoma, as assessed by local laboratory review. (Tissue obtained within 6 months before Day 1 of Cycle 1 will be reviewed by a central independent reviewer to detect pathological type.) Patient has Ann Arbor stage III or IV disease. Exclusion Criteria: Patient has received rituximab (or a rituximab biosimilar), cyclophosphamide, or vincristine. Patient has allergies or hypersensitivity to murine, chimeric, human or humanised proteins, cyclophosphamide, vincristine, or prednisone. Patient has evidence of histological transformation to high-grade or diffuse large B-cell lymphoma. Patient has known central nervous system involvement. Patient has received previous treatment for NHL: Previous treatment including chemotherapy, radiotherapy, immunotherapy, and/or surgery (except previous biopsy) All doses of corticoid therapy for treatment of NHL Corticoid therapy during the previous 4 weeks from Day 1 of Cycle 1 with prednisone >20 mg per day for the treatment for any purpose

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>Patient treated with CT-P10 (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with CT-P10 (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period. | Biological: CT-P10<br> <br> * Other names: Rituximab;Drug: Cyclophosphamide<br> <br> Drug: Vincristine<br> <br> Drug: Prednisone<br> <br> * Other names: Prednisolone;|
| Active Comparator: Rituxan<br>Patient treated with Rituxan (375 mg/m2 IV) in combination with cyclophosphamide (750 mg/m2 IV), vincristine (1.4 mg/m2 [max 2 mg] IV), and prednisone 40 mg/m2 orally) up to 8 cycles every 3 weeks during the Core Study Period. Patients having responses during Core Study Period treated with Rituxan (375 mg/m2 IV) monotherapy up to 12 cycles every 2 months during the Maintenance Study Period. | Biological: Rituxan<br> <br> * Other names: Rituximab;Drug: Cyclophosphamide<br> <br> Drug: Vincristine<br> <br> Drug: Prednisone<br> <br> * Other names: Prednisolone;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum Concentration-time Curve at Steady State (AUCtau) | AUCtau: Area under the plasma drug concentration-time curve within a dosing interval at steady state. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained. | Core Cycle 4 (Week 12) | 
| Maximum Serum Concentration at Steady State (Cmax,ss) | Cmax,ss: Maximum concentration of drug in plasma at steady state on administering a fixed dose at equal dosing intervals. PK sampling was done at pre-dose and 1 hour after the end of infusion (EOI) at Core Cycles 1-3 and 5-8. At Core Cycle 4 (i.e. steady state), intensive PK samplings were done as follows: predose, EOI, 1 hour after EOI, 24 hour after EOI, 168 hour after EOI, 336 hour after EOI, 504 hour after EOI. Lastly, one sample at any time of the end of treatment (EOT) 1 visit was obtained. | Core Cycle 4 (Week 12) | 
| Overall Response Rate (ORR) According to the 1999 International Working Group (IWG) Criteria | ORR was defined as the proportion of patients with the best response of complete response (CR), unconfirmed complete response (CRu), or partial response (PR) by central review. Per 1999 IWG criteria, the disease status was assessed by using contrasted CT, 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 Core Study Period (up to 8 cycles; Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| B-cell Kinetics (B-cell Depletion and Recovery) | B-cell kinetics were demonstrated by median values of B-cell counts (Lower limit of quantification was 20 cells/uL). | Cycles 1 to 8 during the Core Study Period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced Follicular Lymphoma