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

January 19, 2020 updated by: Celltrion

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CT-P10

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.
Drug: Cyclophosphamide
Drug: Prednisone
Other Names:
  • Prednisolone
Drug: Vincristine
Biological: CT-P10
Other Names:
  • Rituximab
Active Comparator: Rituxan

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.
Drug: Cyclophosphamide
Drug: Prednisone
Other Names:
  • Prednisolone
Drug: Vincristine
Biological: Rituxan
Other Names:
  • Rituximab

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)
Time Frame: Core Cycle 4 (Week 12)

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)
Time Frame: Core Cycle 4 (Week 12)

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
Time Frame: During the Core Study Period (up to 8 cycles; Week 24)

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)
Time Frame: Cycles 1 to 8 during the Core Study Period
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Celltrion

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 14, 2014

Primary Completion (Actual)

January 12, 2016

Study Completion (Actual)

December 29, 2018

Study Registration Dates

First Submitted

May 29, 2014

First Submitted That Met QC Criteria

June 10, 2014

First Posted (Estimate)

June 13, 2014

Study Record Updates

Last Update Posted (Actual)

January 29, 2020

Last Update Submitted That Met QC Criteria

January 19, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CT-P10 3.3
  • 2013-004493-96 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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