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

NCT02162771 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: CT-P10 3.32013-004493-96
• Study Type: interventional
• Target: 140
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Lymphoma, Follicular

Keywords

Advanced Follicular Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• B-cell Kinetics (B-cell Depletion and Recovery)

  Cycles 1 to 8 during the Core Study Period

Study Arms (2)

CT-P10

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone

Rituxan

ACTIVE COMPARATOR

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; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone

Interventions

Rituxan BIOLOGICAL

Also known as: Rituximab

Rituxan

CT-P10 BIOLOGICAL

Also known as: Rituximab

CT-P10

Cyclophosphamide DRUG

CT-P10; Rituxan

Vincristine DRUG

CT-P10; Rituxan

Prednisone DRUG

Also known as: Prednisolone

CT-P10; Rituxan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Celltrion: lead

Related Publications (2)

• 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.

  PMID: 28712940 RESULT

• 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.

  PMID: 34477816 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Rituximab; CT-P10; Cyclophosphamide; Vincristine; Prednisone; Prednisolone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Results Point of Contact

• Title: Dr. Sung Hyun Kim
• Organization: CELLTRION, Inc.

contact@celltrion.com

+82-32-850-5000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2014
• First Posted: June 13, 2014
• Study Start: July 14, 2014
• Primary Completion: January 12, 2016
• Study Completion: December 29, 2018
• Last Updated: January 29, 2020
• Results First Posted: January 29, 2020

Record last verified: 2020-01