A Study to Evaluate Safety, Tolerability, PK and PD of HLX01 in Patients With CD20-positive B-cell Lymphomas

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

Detailed Description
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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.

Official Title
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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

Conditions
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B-cell Lymphomas

Intervention / Treatment
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* Drug: HLX01


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLX01 250 mg/m2<br>HLX01 250 mg/m2 administrated intravenously | Drug: HLX01<br>* a potential rituximab biosimilar<br>|
| Experimental: HLX01 375 mg/m2<br>HLX01 375 mg/m2 administrated intravenously | Drug: HLX01<br>* a potential rituximab biosimilar<br>|
| Experimental: HLX01 500 mg/m2<br>HLX01 500 mg/m2 administrated intravenously | Drug: HLX01<br>* a potential rituximab biosimilar<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs | The type, severity and incidence of adverse events | From First infusion to Day 90 | 
| SAEs | Thetype, severity and incidence of SAEs | From First infusion to Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf | Area under the serum concentration-time curve from time 0 extrapolated to infinity | From First administration to Day 90 | 
| Cmax | Maximum serum concentration | From First administration to Day 90 | 
| t1/2 | terminal half-life | From First administration to Day 90 | 
| CD19 positive B cells | The count of CD19 positive in peripheral blood | From First administration to Day 90 | 
| CD20 positive B cells | The count of CD20 positive in peripheral blood | From First administration to Day 90 | 
| Antidrug antibodies of HLX01 | The concentration of anti-HLX01 in serum | From First administration to Day 90 |