search
Back to results

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

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
APG2575
Sponsored by
Ascentage Pharma Group Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, APG-2575

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sun Yat-sen University Cancer Center
  • Zhujiang Hospital of Southern Medical University
  • Nanfang Hospital of Southern Medical University
  • Hainan General Hospital
  • Henan Cancer Hospital
  • Union Hospital medical college Huazhong University of Science and TechnologyRecruiting
  • The First Affilated Hospital of Soochow University
  • People's hospital of Jiangsu Province
  • The First Affilated Hospital of Nanchang University
  • Institute of blood transfusion of Chinese Academy of Medical Sciences
  • The First Affiliated Hospital of Zhejiang University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

APG-2575 single agent in Relapse/Refractory CLL/SLL

Arm Description

APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Progress Free Survival (PFS)
PFS is defined as the time from the first administration to disease progression(PD) or death from any cause.
Time To Progression (TTP)
TTP is defined as the time from the first administration to PD.
Time To Response (TTR)
TTR is defined as the time from the first administration to the subjects' first CR, CRi, or PR.
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.
Overall Survival (OS)
OS is defined as the time from the first administration to death.
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.
Adverse events
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
Maximum plasma concentration (Cmax)
Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2575 treatments.
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.

Full Information

First Posted
November 24, 2021
Last Updated
October 9, 2022
Sponsor
Ascentage Pharma Group Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT05147467
Brief Title
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

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 10, 2022 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
January 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascentage Pharma Group Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, APG-2575

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
APG-2575 single agent in Relapse/Refractory CLL/SLL
Arm Type
Experimental
Arm Description
APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle.
Intervention Type
Drug
Intervention Name(s)
APG2575
Intervention Description
APG-2575 orally once daily at 600mg dose levels, every 28 days as a cycle.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Up to 9 months after the last subject enrolled.
Secondary Outcome Measure Information:
Title
Progress Free Survival (PFS)
Description
PFS is defined as the time from the first administration to disease progression(PD) or death from any cause.
Time Frame
Up to 9 months after the last subject enrolled.
Title
Time To Progression (TTP)
Description
TTP is defined as the time from the first administration to PD.
Time Frame
Up to 9 months after the last subject enrolled.
Title
Time To Response (TTR)
Description
TTR is defined as the time from the first administration to the subjects' first CR, CRi, or PR.
Time Frame
Up to 9 months after the last subject enrolled.
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the subject's first CR, CRi, or PR to PD or death from any cause.
Time Frame
Up to 9 months after the last subject enrolled.
Title
Overall Survival (OS)
Description
OS is defined as the time from the first administration to death.
Time Frame
Up to 9 months after the last subject enrolled.
Title
the time of half absolute lymphocyte value (ALC)
Description
The time of half absolute lymphocyte value (ALC) is defined as the time from the first administration to 50% reduction of ALC of baseline.
Time Frame
Up to 9 months after the last subject enrolled.
Title
Adverse events
Description
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
Time Frame
Up to 9 months after the last subject enrolled.
Title
Maximum plasma concentration (Cmax)
Description
Maximum plasma concentration (Cmax) will be assessed on all participants with APG-2575 treatments.
Time Frame
Up to 4 cycles (each cycle is 28 days).
Title
Area under the plasma concentration versus time curve (AUC)
Description
Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-2575 treatments.
Time Frame
Up to 4 cycles (each cycle is 28 days).
Other Pre-specified Outcome Measures:
Title
Minimal Residual Disease (MRD) negative rate
Description
To observe the proportion of subjects with MRD negative status in bone marrow, peripheral blood, one or both.
Time Frame
Up to 9 months after the last subject enrolled.
Title
Bcl-2 expression
Description
Potential biomarkers to be evaluated included the association of Bcl-2 expression with the efficacy of APG-2575 monotherapy.
Time Frame
Up to 9 months after the last subject enrolled

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zi Chen, Doctor
Phone
+8618117275173
Email
Zi.Chen@ascentage.com
First Name & Middle Initial & Last Name or Official Title & Degree
Min Yu, Doctor
Phone
+8615000679101
Email
Min.Yu@ascentage.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yifan Zhai, MD, PhD
Organizational Affiliation
Ascentage Pharma Group Inc.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jianyong Li, M.D.
Organizational Affiliation
The First Affiliated Hospital with Nanjing Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Liang
First Name & Middle Initial & Last Name & Degree
Yang Liang, Postdoc
Facility Name
Zhujiang Hospital of Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510280
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rui Huang
First Name & Middle Initial & Last Name & Degree
Rui Huang, Ph.D
Facility Name
Nanfang Hospital of Southern Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510515
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ru Feng
First Name & Middle Initial & Last Name & Degree
Ru Feng, M.D.
Facility Name
Hainan General Hospital
City
Haikou
State/Province
Hainan
ZIP/Postal Code
570311
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Li'e Lin
First Name & Middle Initial & Last Name & Degree
Li'e Lin, M.D.
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450003
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Keshu Zhou
First Name & Middle Initial & Last Name & Degree
Keshu Zhou, Ph.D
Facility Name
Union Hospital medical college Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guohui Cui, M.D.
First Name & Middle Initial & Last Name & Degree
Guohui Cui
Facility Name
The First Affilated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caixia Li
First Name & Middle Initial & Last Name & Degree
Caixia Li, Ph.D
Facility Name
People's hospital of Jiangsu Province
City
Suzhou
State/Province
Jiangsu
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianyong Li, M.D.
Email
lijianyonglm@medmail.com.cn
First Name & Middle Initial & Last Name & Degree
Jianyong Li, M.D.
Facility Name
The First Affilated Hospital of Nanchang University
City
Nanchang
State/Province
Jiangxi
ZIP/Postal Code
330006
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Li
First Name & Middle Initial & Last Name & Degree
Fei Li, Ph.D
Facility Name
Institute of blood transfusion of Chinese Academy of Medical Sciences
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
215127
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tingyu Wang
First Name & Middle Initial & Last Name & Degree
Tingyu Wang, Ph.D
Facility Name
The First Affiliated Hospital of Zhejiang University School of Medicine
City
Hanzhou
State/Province
Zhejiang
ZIP/Postal Code
310003
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jie Jin, Ph.D
First Name & Middle Initial & Last Name & Degree
Jie Jin, Ph.D

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs