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

• ClinicalTrials.gov Identifier: NCT02162771
• Recruitment Status: Completed
• First Posted: June 13, 2014
• Results First Posted: January 29, 2020
• Last Update Posted: January 29, 2020
• Sponsor: Celltrion
• Information provided by (Responsible Party): Celltrion

Tracking Information

• First Submitted Date: May 29, 2014
• First Posted Date: June 13, 2014
• Results First Submitted Date: December 26, 2019
• Results First Posted Date: January 29, 2020
• Last Update Posted Date: January 29, 2020
• Actual Study Start Date: July 14, 2014
• Actual Primary Completion Date: January 12, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 19, 2020)

• 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.
• 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.
• 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.

Original Primary Outcome Measures (submitted: June 10, 2014)

Pharmacokinetics [ Time Frame: Week 12 ]

• AUCtau: Area under the serum concentration-time curve at steady state
• CmaxSS: Maximum serum concentration at steady state

Current Secondary Outcome Measures (submitted: January 19, 2020)

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).

Original Secondary Outcome Measures (submitted: June 10, 2014)

Efficacy [ Time Frame: Week 24 ]

Overall response rate(CR + CRu + PR)

• CR: complete response
• CRu: unconfirmed complete response
• PR: partial response

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: To Demonstrate Equivalence of Pharmacokinetics and Noninferiority of Efficacy for CT-P10 in Comparison With Rituxan
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Lymphoma, Follicular

Intervention

• Biological: Rituxan
  Other Name: Rituximab
• Biological: CT-P10
  Other Name: Rituximab
• Drug: Cyclophosphamide
• Drug: Vincristine
• Drug: Prednisone
  Other Name: Prednisolone

Study Arms

• 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.

  Interventions:

  • Biological: CT-P10
  • Drug: Cyclophosphamide
  • Drug: Vincristine
  • Drug: Prednisone
• 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.

  Interventions:

  • Biological: Rituxan
  • Drug: Cyclophosphamide
  • Drug: Vincristine
  • Drug: Prednisone

• Publications *: Kim WS, Buske C, Ogura M, Jurczak W, Sancho JM, Zhavrid E, Kim JS, Hernández-Rivas JÁ, 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 19, 2020): 140
• Original Estimated Enrollment (submitted: June 10, 2014): 250
• Actual Study Completion Date: December 29, 2018
• Actual Primary Completion Date: January 12, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Spain

Administrative Information

• NCT Number: NCT02162771
• Other Study ID Numbers: CT-P10 3.3; 2013-004493-96 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes

• IPD Sharing Statement: Not Provided
• Responsible Party: Celltrion
• Study Sponsor: Celltrion
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Celltrion
• Verification Date: January 2020