Study of APG-2575 in Patients With Relapsed/Refractory CLL/SLL

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of APG-2575 single agent in patients with relapsed/refractory CLL/SLL.

Detailed Description
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This is an single-arm, open-label, multi-center, pivotal registration Phase II study of efficacy and safety of APG-2575 as a single agent in relapsed/refractory CLL/SLL patients. This study plans to enroll approximately 75 CLL/SLL subjects who have failed or are intolerant to prior immunochemotherapy and BTK inhibitor therapy. Eligible subjects will receive APG-2575 600mg, orally administered once daily (QD), within half an hour of a low-fat meal, for a cycle of 28 days. Participants will continue to accept APG - 2575 until the end of treatment that are consistent with the provisions in the solution of the termination of any specified standards.

Official Title
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A Single-arm, Pivotal Registration Phase II Study of the Efficacy and Safety of APG-2575 Monotherapy in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: APG2575


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who meet each of the following inclusion criteria are eligible to participate in this study: Age ≥18 years old. Pathologically confirmed CLL/SLL according to the 2018 revised IWCLL NCI-WG guidelines, subject with measurable lesions or splenomegaly due to CLL. Expected survival is at least 12 weeks. Refractory, recurrent, or intolerant to BTK inhibitors and immunochemotherapy,or first-line treatment with BTK inhibitors fails and is not suitable for immunochemotherapy. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2. Ability to understand and willingness to sign a written informed consent form approved by EC committee (the consent form must be signed by the patient prior to any screening or study-specific procedures). Willingness and ability to comply with study procedures and follow-up examination. Exclusion Criteria: Subjects who meet any of the following exclusion criteria are not to be enrolled in this study: Prior history of allogeneic hematopoietic stem cell transplantation, adoptive cell immunotherapy or autologous hematopoietic stem cell transplantation within 24 months. Failure to recover adequately, at the discretion of the investigator, from prior surgical procedures. Patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry. Received Bcl-2 inhibitor treatment. Invasive NHL transformation or central nervous system (CNS) involvement has occurred. Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of treatment. Within 2 years before entering the study, the subject had a history of active malignant tumors other than CLL / SLL, except that: Fully treated cervical carcinoma in situ; Completely resected basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; Confinement and resection of previously cured malignancies (or other treatment). Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for participation in the study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: APG-2575 single agent in Relapse/Refractory CLL/SLL<br>APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle. | Drug: APG2575<br>* APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined by Complete Remission (CR)+ CR with incomplete marrow recovery (CRi) + Partial Remission (PR) (according to NCI-WG CLL(2018)) and by CR+PR ( according to Lugano (2014)).Response will be evaluated every 2 cycles (8 weeks) till complete treatment or one month after last dose. | Up to 9 months after the last subject enrolled. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progress Free Survival (PFS) | PFS is defined as the time from the first administration to disease progression(PD) or death from any cause. | Up to 9 months after the last subject enrolled. | 
| Time To Progression (TTP) | TTP is defined as the time from the first administration to PD. | Up to 9 months after the last subject enrolled. | 
| Time To Response (TTR) | TTR is defined as the time from the first administration to the subjects' first CR, CRi, or PR. | Up to 9 months after the last subject enrolled. | 
| Duration of Response (DOR) | DOR is defined as the time from the subject's first CR, CRi, or PR to PD or death from any cause. | Up to 9 months after the last subject enrolled. | 
| Overall Survival (OS) | OS is defined as the time from the first administration to death. | Up to 9 months after the last subject enrolled. | 
| the time of half absolute lymphocyte value (ALC) | The time of half absolute lymphocyte value (ALC) is defined as the time from the first administration to 50% reduction of ALC of baseline. | Up to 9 months after the last subject enrolled. | 
| Adverse events | Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0. | Up to 9 months after the last subject enrolled. | 
| Maximum plasma concentration (Cmax) | Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2575 treatments. | Up to 4 cycles (each cycle is 28 days). | 
| Area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-2575 treatments. | Up to 4 cycles (each cycle is 28 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, APG-2575