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Evaluate the Efficacy and Safety of HLX01 Versus Mabthera in Patients With Low Tumour Burden Follicular Lymphoma.

Primary Purpose

CD20-positive Follicular Lymphoma, With Low Tumour Burden

Status

Withdrawn

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

HLX01

Mabthera®

About this trial

This is an interventional treatment trial for CD20-positive Follicular Lymphoma, With Low Tumour Burden

Eligibility Criteria

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

Inclusion Criteria:

Voluntary written informed consent before any study-related activities
≥ 18 years of age
Histologically-confirmed, stage II to IV NHL (CD20+ FL of grades 1, 2, or 3a) by World Health Organization classification of lymphoid neoplasms (2016 revision) [11]
Low tumour burden according to the GELF criteria
The Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Availability of tumour sample within 12 months before start of study drug treatment
At least 1 bi-dimensionally measurable nodal lesion >1.5 cm or extranodal lesion >1 cm in its longest diameter by CT scan as defined by the Modified Lugano Response Classification 2014
Adequate organ function

Exclusion Criteria:

Prior treatment for FL. Patients previously treated with radiotherapy for stage I FL may be eligible provided they have a measurable lesion located outside the radiation field
Transformation to high-grade lymphoma
Patients with advanced disease that are considered for treatment with combined chemo immunotherapy
Presence or history of central nervous system (CNS) lymphoma involvement
Treatment with an investigational agent within 28 days of the first dose of study drug infusion
Prior treatment with a chimeric antibody, including HLX01 and Mabthera®
History of another malignancy within 2 years of screening, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ of the uterine cervix, breast or bladder, localised prostate cancer stage T1c or less - and provided that the patient remains relapse free
Major surgery within 28 days of the first dose of study drug infusion (excluding lymph node biopsy)
Known human immunodeficiency virus (HIV) infection (Serological test for HIV should be performed at screen unless prohibited by local regulations)
Active and/or severe infections, including any ongoing infection requiring IV anti microbial treatment
Have a current diagnosis of active tuberculosis
Active HBV and a positive serological test for HBV (except seropositive due to HBV vaccination) or hepatitis C virus (HCV)
Ongoing immunosuppressant treatment; corticosteroid treatment exceeding 20 mg/day prednisone or equivalent within 7 days of the first dose of study drug infusion
Known hypersensitivity or allergy to the active principle and/or formulations' ingredients; history of severe allergy or anaphylaxis to murine or biologic agents
Live or live attenuated vaccine within 28 days of the first dose of study drug infusion
History of significant cardiac or vascular disease including, but not limited to: history of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within 6 months before randomisation; congestive heart failure according to the New York Heart Association (NYHA) Functional Classification class III or IV

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HLX01

EU-sourced rituximab (Mabthera®)

Arm Description

Outcomes

Primary Outcome Measures

Overall Response Rate

Overall Response Rate up to Week 28, defined as the proportion of patients achieving either complete response (CR) or PR as best response from the first dose of study drug through Week 28 as assessed by a blinded independent review committee according to the Modified Lugano Response Classification 2014.

Secondary Outcome Measures

AEs

adverse events

SAEs

serious adverse events

Immunogenicity

ADA and neutralising antibody

Time-to-progression of disease (TTPD)

Time-to-progression of disease

PFS

progression-free survival

Cmax

max blood cocentration

Ctrough

trough serum concentration after each dose during induction period and selected doses thereafter

Full Information

NCT ID

NCT04671420

First Posted

March 30, 2020

Last Updated

December 10, 2020

Sponsor

Shanghai Henlius Biotech

1. Study Identification

Unique Protocol Identification Number

NCT04671420

Brief Title

Evaluate the Efficacy and Safety of HLX01 Versus Mabthera in Patients With Low Tumour Burden Follicular Lymphoma.

Official Title

A Phase 3 Multi-Centre, Randomised, Double-Blind, Parallel-Arm Study to Evaluate the Efficacy and Safety of HLX01 Versus Rituximab (Mabthera®) as First Line Treatment in Patients With Low Tumour Burden Follicular Lymphoma.

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Withdrawn

Why Stopped

sponsor strategy decision

Study Start Date

October 2020 (Anticipated)

Primary Completion Date

April 2022 (Anticipated)

Study Completion Date

October 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Shanghai Henlius Biotech

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The study is a Phase 3 multi-centre, randomised, double-blind, parallel-arm study to evaluate the efficacy and safety of HLX01 versus European Union (EU)-sourced Mabthera® as first line treatment in patients with low tumour burden FL. The study will consist of a Screening Period (up to 42 days), Treatment Period (Week 1 to Week 44/Month 11), and End of Study (EOS; Month 12 Visit). Approximately 212 patients (106 in each treatment group) will be enrolled. Utilising a 1-sided 97.5% CI for the risk difference, a reference proportion of 83.2% for Mabthera®, delta for non-inferiority of -17%, and assuming a true difference of 1%, a sample size of 106 patients per arm (212 total) provides approximately 85% power to show non-inferiority of HLX01 to Mabthera® on a primary endpoint of risk difference in ORR up to Week 28. No dropout is included, as all patients will either have data provided for ORR (based on best response), or will be classed as non-responder.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

CD20-positive Follicular Lymphoma, With Low Tumour Burden

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

HLX01

Arm Type

Experimental

Arm Title

EU-sourced rituximab (Mabthera®)

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

HLX01

Intervention Description

Patients will receive HLX01 intravenous (IV) infusion once a week for 4 weeks induction treatment (on Days 1, 8, 15, and 22), and then continue to receive maintenance treatment at Weeks 12, 20, 28, 36, and 44.

Intervention Type

Drug

Intervention Name(s)

Mabthera®

Intervention Description

Patients will receive Mabthera® intravenous (IV) infusion once a week for 4 weeks induction treatment (on Days 1, 8, 15, and 22), and then continue to receive maintenance treatment at Weeks 12, 20, 28, 36, and 44.

Primary Outcome Measure Information:

Title

Overall Response Rate

Description

Time Frame

rom the first dose of study drug through Week 28

Secondary Outcome Measure Information:

Title

AEs

Description

adverse events

Time Frame

up to 12 months

Title

SAEs

Description

serious adverse events

Time Frame

up to 12 months

Title

Immunogenicity

Description

ADA and neutralising antibody

Time Frame

up to 12 months

Title

Time-to-progression of disease (TTPD)

Description

Time-to-progression of disease

Time Frame

up to 12 months

Title

PFS

Description

progression-free survival

Time Frame

up to 12 months

Title

Cmax

Description

max blood cocentration

Time Frame

up to 12 months

Title

Ctrough

Description

trough serum concentration after each dose during induction period and selected doses thereafter

Time Frame

up to 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Voluntary written informed consent before any study-related activities ≥ 18 years of age Histologically-confirmed, stage II to IV NHL (CD20+ FL of grades 1, 2, or 3a) by World Health Organization classification of lymphoid neoplasms (2016 revision) [11] Low tumour burden according to the GELF criteria The Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Availability of tumour sample within 12 months before start of study drug treatment At least 1 bi-dimensionally measurable nodal lesion >1.5 cm or extranodal lesion >1 cm in its longest diameter by CT scan as defined by the Modified Lugano Response Classification 2014 Adequate organ function Exclusion Criteria: Prior treatment for FL. Patients previously treated with radiotherapy for stage I FL may be eligible provided they have a measurable lesion located outside the radiation field Transformation to high-grade lymphoma Patients with advanced disease that are considered for treatment with combined chemo immunotherapy Presence or history of central nervous system (CNS) lymphoma involvement Treatment with an investigational agent within 28 days of the first dose of study drug infusion Prior treatment with a chimeric antibody, including HLX01 and Mabthera® History of another malignancy within 2 years of screening, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ of the uterine cervix, breast or bladder, localised prostate cancer stage T1c or less - and provided that the patient remains relapse free Major surgery within 28 days of the first dose of study drug infusion (excluding lymph node biopsy) Known human immunodeficiency virus (HIV) infection (Serological test for HIV should be performed at screen unless prohibited by local regulations) Active and/or severe infections, including any ongoing infection requiring IV anti microbial treatment Have a current diagnosis of active tuberculosis Active HBV and a positive serological test for HBV (except seropositive due to HBV vaccination) or hepatitis C virus (HCV) Ongoing immunosuppressant treatment; corticosteroid treatment exceeding 20 mg/day prednisone or equivalent within 7 days of the first dose of study drug infusion Known hypersensitivity or allergy to the active principle and/or formulations' ingredients; history of severe allergy or anaphylaxis to murine or biologic agents Live or live attenuated vaccine within 28 days of the first dose of study drug infusion History of significant cardiac or vascular disease including, but not limited to: history of stroke, unstable angina, myocardial infarction or ventricular arrhythmia requiring medication or mechanical control within 6 months before randomisation; congestive heart failure according to the New York Heart Association (NYHA) Functional Classification class III or IV

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Evaluate the Efficacy and Safety of HLX01 Versus Mabthera in Patients With Low Tumour Burden Follicular Lymphoma.

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