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

NCT04671420 | Withdrawn Phase 3 DMC

• 1 other identifier: HLX01-FL03
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

CD20-positive Follicular Lymphoma, With Low Tumour Burden

Outcome Measures

Primary Outcomes (1)

• 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.

  rom the first dose of study drug through Week 28

Secondary Outcomes (7)

• AEs

  up to 12 months

• SAEs

  up to 12 months

• Immunogenicity

  up to 12 months

• Time-to-progression of disease (TTPD)

  up to 12 months

• PFS

  up to 12 months

Study Arms (2)

HLX01

EXPERIMENTAL

Drug: HLX01

EU-sourced rituximab (Mabthera®)

ACTIVE COMPARATOR

Drug: Mabthera®

Interventions

HLX01 DRUG

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.

HLX01

Mabthera® DRUG

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.

EU-sourced rituximab (Mabthera®)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Henlius Biotech: lead

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: March 30, 2020
• First Posted: December 17, 2020
• Study Start: October 1, 2020
• Primary Completion: April 1, 2022
• Study Completion: October 1, 2022
• Last Updated: December 17, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share