Clinical trial NCT03218072: A Study to Evaluate Safety, Tolerability, PK and PD of HLX01 in Patients With CD20-positive B-cell Lymphomas
Official title: A Phase Ia, Multi-centers, Open-label, Dose-escalation Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HLX01 (a Potential Rituximab Biosimilar) in Patients With CD20-positive B-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Lymphomas
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2017-07-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01 (a potential rituximab biosimilar) in patients with CD20-positive B-cell lymphomas.

Detailed description: This was a phase Ia, multicenter, open-label, dose-escalation clinical study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics characteristics of HLX01 injection in patients with CD20-positive B-cell lymphomas.

Eligibility criteria: Inclusion Criteria:

* 18 years ≤ aged ≤ 65 years, male or female;
* having histologically confirmed diagnosis of relapsed/refractory CD20-positive B-cell lymphomas which needed consolidation therapy;
* Eastern Cooperative Oncology Group (ECOG) performance status≤1 and life expectancy ≥3 months;
* providing signed and dated informed consents.

Exclusion Criteria:

* Usage of rituximab or other anti-CD20 monoclonal antibody within 2 years before enrollment;
* usage of hematopoietic cytokines within 1 week before enrollment, e.g. granulocyte colony stimulating factor (G-CSF);
* recent major surgery (excluding diagnostic surgery) within the past 8 weeks;
* peripheral nervous system diseases or central nervous system diseases;
* inadequate hematologic function met any of the following at screening: white blood cell count \<3.0×109/L, absolute neutrophil count (lobocyte and rhabdocyte) \<1.5×109/L, platelet count \<100×109/L, hemoglobin \<90 g/L, for patients with bone marrow involvement, absolute neutrophil count (lobocyte and rhabdocyte) \<1.0×109/L, platelet count \<75×109/L, hemoglobin \<80 g/L;
* inadequate liver function met any of the following at screening: total bilirubin\>1.5×the upper limit of normal range (ULN), ALT or AST\>2.0×ULN, alkaline phosphatase (ALP)\>3.0×ULN;
* abnormal renal function (serum creatinine\>1.5×ULN);
* abnormal thyroid function (TSH\< lower limit of normal or \> upper limit of normal with clinical significance judged by investigators);
* positive test result(s) for serum HIV antigen or antibody;
* seropositivity of HBsAg, or seropositivity of HBcAb and HBV DNA\>ULN; seropositivity of Anti HCV antibody;
* history of herpes zoster and left with sequelae or latent infection;
* other serious disease which may restrict subjects to participate in the trial (such as ongoing active infection, uncontrolled diabetes mellitus, severe cardiac insufficiency or angina pectoris, gastric ulcer, active autoimmune disease, etc.);
* pregnancy or breast feeding female, or not willing to use effective contraceptive measures during the study;
* allergic constitution, or known allergic to components of rituximab or other anti-CD20 monoclonal antibody;
* history of alcoholism or drug abuse; participation in other clinical trials within 3 months before enrollment;
* not suitable for enrollment at investigator's discretion.

Primary outcomes:
measure: AEs
timeFrame: From First infusion to Day 90
measure: SAEs
timeFrame: From First infusion to Day 90
Secondary outcomes:
measure: AUC0-inf
timeFrame: From First administration to Day 90
measure: Cmax
timeFrame: From First administration to Day 90
measure: t1/2
timeFrame: From First administration to Day 90
measure: CD19 positive B cells
timeFrame: From First administration to Day 90
measure: CD20 positive B cells
timeFrame: From First administration to Day 90
measure: Antidrug antibodies of HLX01
timeFrame: From First administration to Day 90
Other outcomes:
Locations:
Study officials:
References:
citation: Shi Y, Zhang Q, Han X, Qin Y, Ke X, Su H, Liu L, Fu J, Jin J, Feng J, Hong X, Zhang X, Wu D, Jiang B, Dong X. Phase 1 studies comparing safety, tolerability, pharmacokinetics and pharmacodynamics of HLX01 (a rituximab biosimilar) to reference rituximab in Chinese patients with CD20-positive B-cell lymphoma. Chin J Cancer Res. 2021 Jun 30;33(3):405-416. doi: 10.21147/j.issn.1000-9604.2021.03.11.