Lymphoma, FollicularPhase 3rituximabNCT02162771

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

A Phase 3 study testing Rituxan, CT-P10 and Cyclophosphamide in people with Lymphoma, Follicular, run by Celltrion.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Lymphoma, Follicular
What is being tested?: Rituxan, CT-P10 and Cyclophosphamide
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 140 participants
Where: No sites listed yet
Study dates: 14 Jul 2014to 29 Dec 2018
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

About this study

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
Being tested: Rituxan, CT-P10, Cyclophosphamide, Vincristine, Prednisone
Keywords: Advanced Follicular Lymphoma
Medical subject headings: Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RituxanBiological
Also called Rituximab
CT-P10Biological
Also called Rituximab
CyclophosphamideDrug
VincristineDrug
PrednisoneDrug
Also called Prednisolone

Study groups in NCT02162771
Study group	Role	What they receive
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. Receives: 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. Receives: Biological: Rituxan; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: During the Core Study Period (up to 8 cycles; Week 24)

Secondary outcomes (1)

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).
Measured: Cycles 1 to 8 during the Core Study Period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Jul 201429 Dec 2018

First posted13 Jun 2014 (estimated)
Study start14 Jul 2014
Primary completion12 Jan 2016
Study completion29 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Lymphoma, FollicularStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 140 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02162771
Sponsor's protocol ID: CT-P10 3.3
Other IDs: 2013-004493-96
Acronym: rituximab
Status last verified: Jan 2020
First submitted: 29 May 2014
Last updated: 29 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes

Publications

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.
PubMed 28712940
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.
PubMed 34477816

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingPhase 1/2
A Platform Trial Evaluating New Drugs or Combination in R/R Peripheral T-cell Lymphomas
Peripheral T Cells Lymphoma (PTCL), Follicular Helper T-Cell Lymphoma
Active, not recruiting
EXHIT ENTRE Implementation Trial of High Intensity Versus Low Intensity Strategy
Substance Use Disorders, Opioid Use Disorder, Severe
RecruitingPhase 1/2
Dose Escalation and Dose Expansion Study of MDX2003 in Patients With Different Types of Lymphoma
Lymphoma, Waldenström Macroglobulinemia (WM)
Active, not recruitingPhase 1
A Rollover Study of CC-122
Non-Hodgkin Lymphoma
Recruiting
STEpwise Research Program to Promote INGeniouS ONline Supportive Solutions in the Relief of Cancer-related Fatigue
Cancer Diagnosis, Moderate or Severe Score of Cancer-related Fatigue (CRF)

All Lymphoma, Follicular trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02162771
Acronym / sponsor ID: rituximab / CT-P10 3.3
Conditions: Lymphoma, Follicular
Keywords: Advanced Follicular Lymphoma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 140 participants (actual)
Lead sponsor: CelltrionIndustry (pharma, biotech, devices)
Study start: 14 Jul 2014 (actual)
Primary completion: 12 Jan 2016 (actual)
Study completion: 29 Dec 2018 (actual)
First posted: 13 Jun 2014 (estimated)
Results: Posted 29 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
CT-P10	Experimental	Biological: CT-P10, Drug: Cyclophosphamide, Drug: Vincristine, Drug: PrednisonePatient 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.
Rituxan	Active comparator	Biological: Rituxan, Drug: Cyclophosphamide, Drug: Vincristine, Drug: PrednisonePatient 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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:
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.

Key exclusion criteria (8 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RituxanAlso: Rituximab	Biological	Rituxan
CT-P10Also: Rituximab	Biological	CT-P10
Cyclophosphamide	Drug	CT-P10, Rituxan
Vincristine	Drug	CT-P10, Rituxan
PrednisoneAlso: Prednisolone	Drug	CT-P10, Rituxan

Primary outcome

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.

1 secondary outcome

B-cell Kinetics (B-cell Depletion and Recovery)
Time frame: Cycles 1 to 8 during the Core Study Period

Results and safety

Results posted to the registry on 29 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CT-P10	70	62
Rituxan	70	62

Primary outcome: Area Under the Serum Concentration-time Curve at Steady State (AUCtau)

Time frame: Core Cycle 4 (Week 12). Geometric mean (Standard Error). Unit: h*ug/mL

Measure	CT-P10 n = 50	Rituxan n = 56
Value	41002.43 (1.136)	40099.08 (1.143)

CT-P10 vs Rituxan: Ratio of geometric least square means: 102.25 (90% CI 94.05 to 111.17), ANCOVA

Population analysed: Pharmacokinetic Population consisted of all patients who had at least 1 posttreatment PK concentration result after receiving at least 1 dose of study drug (CT-P10 or Rituxan) in Part 1. Patients considered outliers identified by a robust regression model (95% CI) were excluded from the analysis.

Primary outcome: Maximum Serum Concentration at Steady State (Cmax,ss)

Time frame: Core Cycle 4 (Week 12). Geometric mean (Standard Error). Unit: ug/mL

Measure	CT-P10 n = 53	Rituxan n = 56
Value	256.19 (1.115)	254.49 (1.120)

CT-P10 vs Rituxan: Ratio of geometric least square means: 100.67 (90% CI 93.84 to 108.00), ANCOVA

Primary outcome: 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). Count of participants. Unit: Participants

Measure	CT-P10 n = 66	Rituxan n = 68
Value	64	63

CT-P10 vs Rituxan: Point estimate difference: 4.3

Population analysed: Efficacy population consisted of all patients who had at least 1 response evaluation after receiving at least 1 treatment cycle in the Core Study Period without any major protocol deviation that was relevant to the efficacy endpoint in Part 2.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Adverse events (AEs) and Serious adverse events (SAEs) were to be collected from the date the ICF was signed until up to 30 days from last dose of the study drug, regardless of relationship to the study drug (a median follow up of 39.9 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CT-P10	24 of 70 (34.3%)	58 of 70 (82.9%)	Not reported
Rituxan	13 of 70 (18.6%)	57 of 70 (81.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 28712940Kim 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.
Derived from this study: PubMed 34477816Buske 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.
Related InfoLink provided by the sponsor.

Related trials for Lymphoma, Follicular

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituxan, CT-P10 and Cyclophosphamide in people with Lymphoma, Follicular, run by Celltrion.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Serum Concentration-time Curve at Steady State (AUCtau) (time frame: Core Cycle 4 (Week 12)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02162771, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2020.