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

Primary Purpose

Lymphoma, Follicular

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Rituxan
CT-P10
Cyclophosphamide
Vincristine
Prednisone
Sponsored by
Celltrion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, Follicular focused on measuring Advanced Follicular Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patient is male or female older than 18 years.
  2. Patient has histologically confirmed FL according to the World Health Organization 2008 classification (Jaffe 2009); grades 1 to 3a based on local laboratory review.

  3. 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
  4. 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.)
  5. Patient has Ann Arbor stage III or IV disease.

Exclusion Criteria:

  1. Patient has received rituximab (or a rituximab biosimilar), cyclophosphamide, or vincristine.
  2. Patient has allergies or hypersensitivity to murine, chimeric, human or humanised proteins, cyclophosphamide, vincristine, or prednisone.
  3. Patient has evidence of histological transformation to high-grade or diffuse large B-cell lymphoma.
  4. Patient has known central nervous system involvement.

  5. 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    CT-P10

    Rituxan

    Arm Description

    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.

    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.

    Outcomes

    Primary Outcome Measures

    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.
    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.
    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.

    Secondary Outcome Measures

    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).

    Full Information

    First Posted
    May 29, 2014
    Last Updated
    January 19, 2020
    Sponsor
    Celltrion
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02162771
    Brief Title
    To Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan
    Acronym
    rituximab
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2020
    Overall Recruitment Status
    Completed
    Study Start Date
    July 14, 2014 (Actual)
    Primary Completion Date
    January 12, 2016 (Actual)
    Study Completion Date
    December 29, 2018 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Celltrion

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Lymphoma, Follicular
    Keywords
    Advanced Follicular Lymphoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    140 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    CT-P10
    Arm Type
    Experimental
    Arm Description
    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.
    Arm Title
    Rituxan
    Arm Type
    Active Comparator
    Arm Description
    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.
    Intervention Type
    Biological
    Intervention Name(s)
    Rituxan
    Other Intervention Name(s)
    Rituximab
    Intervention Type
    Biological
    Intervention Name(s)
    CT-P10
    Other Intervention Name(s)
    Rituximab
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide
    Intervention Type
    Drug
    Intervention Name(s)
    Vincristine
    Intervention Type
    Drug
    Intervention Name(s)
    Prednisone
    Other Intervention Name(s)
    Prednisolone
    Primary Outcome Measure Information:
    Title
    Area Under the Serum Concentration-time Curve at Steady State (AUCtau)
    Description
    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.
    Time Frame
    Core Cycle 4 (Week 12)
    Title
    Maximum Serum Concentration at Steady State (Cmax,ss)
    Description
    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.
    Time Frame
    Core Cycle 4 (Week 12)
    Title
    Overall Response Rate (ORR) According to the 1999 International Working Group (IWG) Criteria
    Description
    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.
    Time Frame
    During the Core Study Period (up to 8 cycles; Week 24)
    Secondary Outcome Measure Information:
    Title
    B-cell Kinetics (B-cell Depletion and Recovery)
    Description
    B-cell kinetics were demonstrated by median values of B-cell counts (Lower limit of quantification was 20 cells/uL).
    Time Frame
    Cycles 1 to 8 during the Core Study Period

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    28712940
    Citation
    Kim WS, Buske C, Ogura M, Jurczak W, Sancho JM, Zhavrid E, Kim JS, Hernandez-Rivas JA, Prokharau A, Vasilica M, Nagarkar R, Osmanov D, Kwak LW, Lee SJ, Lee SY, Bae YJ, Coiffier B. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol. 2017 Aug;4(8):e362-e373. doi: 10.1016/S2352-3026(17)30120-5. Epub 2017 Jul 14.
    Results Reference
    result
    PubMed Identifier
    34477816
    Citation
    Buske C, Jurczak W, Sancho JM, Zhavrid E, Kim JS, Hernandez-Rivas JA, Prokharau A, Vasilica M, Nagarkar R, Kwak L, Kim WS, Lee S, Kim S, Ahn K, Ogura M. Long-term efficacy and safety of CT-P10 or rituximab in untreated advanced follicular lymphoma: a randomized phase 3 study. Blood Adv. 2021 Sep 14;5(17):3354-3361. doi: 10.1182/bloodadvances.2021004484.
    Results Reference
    derived
    Links:
    URL
    http://www.celltrion.com
    Description
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