Clinical trial NCT05147467: Study of APG-2575 in Patients With Relapsed/Refractory CLL/SLL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
APG-2575
Lead sponsor: Ascentage Pharma Group Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-07
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

Subjects who meet each of the following inclusion criteria are eligible to participate in this study:

1. Age ≥18 years old.
2. Pathologically confirmed CLL/SLL according to the 2018 revised IWCLL NCI-WG guidelines, subject with measurable lesions or splenomegaly due to CLL.
3. Expected survival is at least 12 weeks.
4. Refractory, recurrent, or intolerant to BTK inhibitors and immunochemotherapy,or first-line treatment with BTK inhibitors fails and is not suitable for immunochemotherapy.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -2.
6. 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).
7. 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:

1. Prior history of allogeneic hematopoietic stem cell transplantation, adoptive cell immunotherapy or autologous hematopoietic stem cell transplantation within 24 months.
2. 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.
3. Received Bcl-2 inhibitor treatment.
4. Invasive NHL transformation or central nervous system (CNS) involvement has occurred.
5. Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of treatment.
6. 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).
7. Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for participation in the study.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 9 months after the last subject enrolled.
Secondary outcomes:
measure: Progress Free Survival (PFS)
timeFrame: Up to 9 months after the last subject enrolled.
measure: Time To Progression (TTP)
timeFrame: Up to 9 months after the last subject enrolled.
measure: Time To Response (TTR)
timeFrame: Up to 9 months after the last subject enrolled.
measure: Duration of Response (DOR)
timeFrame: Up to 9 months after the last subject enrolled.
measure: Overall Survival (OS)
timeFrame: Up to 9 months after the last subject enrolled.
measure: the time of half absolute lymphocyte value (ALC)
timeFrame: Up to 9 months after the last subject enrolled.
measure: Adverse events
timeFrame: Up to 9 months after the last subject enrolled.
measure: Maximum plasma concentration (Cmax)
timeFrame: Up to 4 cycles (each cycle is 28 days).
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Up to 4 cycles (each cycle is 28 days).
Other outcomes:
measure: Minimal Residual Disease (MRD) negative rate
timeFrame: Up to 9 months after the last subject enrolled.
measure: Bcl-2 expression
timeFrame: Up to 9 months after the last subject enrolled
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital medical college Huazhong University of Science and Technology
state: Hubei
city: Suzhou
country: China
facility: The First Affilated Hospital of Soochow University
state: Jiangsu
city: Suzhou
country: China
facility: People's hospital of Jiangsu Province
state: Jiangsu
city: Nanchang
country: China
facility: The First Affilated Hospital of Nanchang University
state: Jiangxi
city: Tianjin
country: China
facility: Institute of blood transfusion of Chinese Academy of Medical Sciences
state: Tianjin
city: Hanzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Ascentage Pharma Group Inc.
name: Yifan Zhai, MD, PhD
role: STUDY_DIRECTOR
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Jianyong Li, M.D.
role: PRINCIPAL_INVESTIGATOR
References: