ICP-022 Versus Chlorambucil Combined With Rituximab in the Treatment of Untreated CLL/SLL

Study Overview
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Brief Summary
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This is a randomized, multicenter, open-label, Phase 3 study to evaluate the efficacy and safety of ICP-022 versus Chlorambucil plus Rituximab in subjects with Previously Untreated Chronic Lymphocytic Leukemia.

Official Title
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A Randomized, Controlled, Open, Multicenter Phase 3 Study to Evaluate ICP-022 Versus Chlorambucil Combined With Rituximab for Primary Treatment of Chronic Lymphocytic Leukemia(CLL)/ Small Lymphocytic Lymphoma(SLL)

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: ICP-022
* Drug: Chlorambucil
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female, age ≥65 years old or age >18 years old or <65 years old, age >18 years old or <65 years old shall meet any of the following criteria simultaneously: A.Disease accumulation score (CIRS) > 6;B. Creatinine clearance at 30-69 mL/ min (Cockcroft-Gault assessment) Enhanced computed tomography/magnetic resonance imaging (CT/MRI) detection had measurable lesions: at least one lymph node had a maximum axis of more than 1.5 cm and had a measurable vertical dimension ECOG physical strength score is 0-2. Expected survival time >6 months. Voluntary written informed consent prior to screening. Key Exclusion Criteria: Patients with stroke or intracranial hemorrhage in the first 6 months were randomly assigned. Hypersensitivity to ICP-022, nitrogen mustard benzoate, rituximab or any other component of the applicable study drug. Any mental or cognitive impairment that may limit their understanding of the informed consent, their implementation and their compliance with the study. Pregnant and lactating women, or subjects of childbearing age who do not want to use contraception within 180 days from the end of the study period to the end of the study period. Conditions in which a potentially life-threatening illness or severe organ dysfunction is not considered appropriate by the investigator. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICP-022<br>ICP-022 will be orally administered until disease progression or unacceptable toxicity. | Drug: ICP-022<br>* ICP-022 at a dose of 150mg, QD<br>|
| Active Comparator: Chlorambucil combined with Rituximab<br>Chlorambucil orally administered and Rituximab via IV infusion for 6 cycles. | Drug: Chlorambucil<br>* 0.5 mg/kg body weight orally on Day 1 and Day 15 of Cycles 1-6<br>Drug: Rituximab<br>* 375 mg/m2 IV infusion on Day 1 of Cycle 1. 500 mg/m2 IV infusion on Day 1 for each of subsequent cycles (Cycles 2-6)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Progress-free survival (PFS) was evaluated by the independent review board (IRC) against the IWCLL2018 criteria (Hallek et al., 2018) and the revised lymphoma mitigation assessment criteria (Cheson et al., 2014). | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | Up to 5 years | 
| Duration Of Response (DOR) |  | Up to 5 years | 
| Overall Survival (OS) |  | Up to 5 years |