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Chronic Lymphocytic LeukemiaPhase 1/2NCT04494503

Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL

A Phase 1/2 study testing APG-2575, Rituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Ascentage Pharma Group Inc. at 18 sites in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this study is to assess the safety, pharmacokinetic, pharmacodynamic and efficacy of APG-2575 single agent and in combination with other therapeutic agents in patients with relapsed/refractory CLL/SLL. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
APG-2575, Rituximab and Ibrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
123 participants
Where
18 sitesChina
Study dates
31 Aug 2020to Dec 2025
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects who meet each of the following inclusion criteria are eligible to participate in this study:
  • Age ≥18 years old.
  • Diagnosis as relapsed/refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma according to the IWCLL NCI-WG guidelines revised in 2008.
  • Through radiological assessment, subjects with a lymph node length ≥ 10 cm require prior approval from the sponsor before enrollment.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1.
  • QTcF interval ≤450ms in males, and ≤470ms in females.
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  • Adequate bone marrow function independent of growth factor and transfusion.
  • Adequate renal and liver function.
  • Willingness by males, female patients of child bearing potential, and their partners to use contraception by effective methods throughout the treatment period and for at least three months following the last dose of study drug.
  • Pregnancy test results of serum samples obtained within 14 days before the first study drug administration in fertile female subjects were negative; If the serum pregnancy test results obtained are> 7 days from the first administration, urine sample obtained before the first study dose of study drug must be negative.
  • Male subjects must avoid sperm donation throughout the treatment period and for at least three months following the last dose of study drug.
  • 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.

Who cannot join

  • Patients 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 within 24 months or autologous hematopoietic stem cell transplantation within 12 months.
  • Monoclonal antibody therapy against CLL was adopted within 4 weeks prior to the first dose of the study drug.
  • Receive any of the following treatments within 14 days or 5x half-life before the first dose of study drug, or clinically significant adverse reactions / toxicities due to previous treatments have not recovered to ≤ Grade 1: Anti-tumor therapies include chemotherapy, radiotherapy, anti-tumor steroid treatment, anti-tumor Chinese medicine treatment; investigational treatment, including targeted small molecule drugs.
  • Use the following drugs within 14 days before the first dose of study drug: moderately potent CYP3A inhibitors such as fluconazole, ketoconazole and clarithromycin; moderately potent CYP3A inducers such as rifampin, carbamazepine, phenytoin And St. John's wort.
  • 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.
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  • Received Bcl-2 inhibitor treatment.
  • Invasive NHL transformation or central nervous system (CNS) involvement. has occurred.
  • Cardiovascular disease of grade ≥2 (New York Heart Association Class).
  • A significant history of renal, neurological, psychiatric, pulmonary, endocrine, metabolic, immune, cardiovascular or liver disease. The investigator believes that participating in this study will have an adverse effect on him / her. For subjects requiring intervention for any of the above diseases in the past 6 months, the investigator and the sponsor must discuss.
  • Warfarin or other anticoagulants is required.
  • Known to be allergic to study drug ingredients or their analogues.
  • Pregnancy or lactation, or pregnancy is expected during the study period or within 3 months after the last administration of treatment.
  • Within 3 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).
  • Has malabsorption syndrome or other conditions that are not suitable for enteral administration.
  • Uncontrolled other clinically significant symptoms, including but not limited to: uncontrolled systemic infections (viruses, bacteria, or fungi), including but not limited to known hepatitis B virus (HBV) surface antigens and DNA positive(HBV-DNA≥2000copies/mL or ≥500IU/mL); Hepatitis C virus (HCV) antibody positive or RNA positive; human immunodeficiency virus (HIV) antibody positive; Febrile neutropenia occured within 1 week before administration.
  • Primary active autoimmune diseases and connective tissue diseases, such as active and uncontrolled primary autoimmune hemocytopenia, including autoimmune hemolytic anemia (AIHA) and primary immune thrombocytopenia (ITP).
  • Any other condition or circumstance that would, at the discretion of the investigator, make the patient unsuitable for participation in the study.

Trial locations and contacts

18 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Jianyong Li, M.D. contact

+86-25-83781120

lijianyonglm@medmail.com.cn

18 sites in 1 country

China18 sites, 18 recruiting

  • Peking University Third Hospital

    Beijing, Beijing Municipality

    Hongmei Jing, M.D.

    Recruiting

  • Xiangya Hospital Central South University

    Changsha, Hunan

    Xielan Zhao, M.D.

    Recruiting

  • Chongqing Cancer Hospital

    Chongqing, Chongqing Municipality

    Yi Gong, M.D., Ph.D.

    Recruiting

  • Nanfang Hospital of Southern Medical University

    Guangzhou, Guangdong

    Chongyuan Xu Professor, +86+020-62786845, nfyygcp@126.com

    Ru Feng Professor

    Recruiting

  • The Affiliated Hospital of Guizhou Medical University

    Guiyang, Guizhou

    Jishi Wang, Doctor

    Recruiting

  • The First Bethune Hospital of Jilin University

    Hangzhou, Zhejiang

    Jie Jin, Doctor

    Recruiting

  • The Second Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang

    Wenbin Qian, Doctor

    Recruiting

  • The First affiliated hospital of Nanchang University

    Nanchang, Jiangxi

    Li Professor

    Recruiting

  • The First Affiliated Hospital of Nanjing Medical University

    Nanjing, Jiangsu

    Jianyong Li, M.D., lijianyonglm@medmail.com.cn

    Recruiting

  • Zhongda Hospital Southeast University

    Nanjing, Jiangsu

    Xiaoping Zhang, M.D.

    Recruiting

  • Guangxi Medical University Affiliated Tumor Hospital

    Nanning, Guangxi

    Hong Cen, Doctor

    Recruiting

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality

    Fangfang LV, Master

    Dongmei Ji, Doctor

    Recruiting

  • Fudan University Zhongshan Hospital

    Shanghai, Shanghai Municipality

    Peng Liu, M.D.

    Not yet recruiting

  • The Fourth Hospital of Hebei Medical University

    Shijiazhuang, Hebei

    Lihong Liu, M.D.

    Recruiting

  • The First affiliated hospital of Soochow University

    Suzhou, Jiangsu

    Caixia Li, M.D., +86-0512-67781856, suzhouhematology@163.com

    Recruiting

  • Blood Diseases Hospital Chinese Academy of Medical Sciences

    Tianjin, Tianjin Municipality

    Shuhua Yi, Doctor

    Recruiting

  • Union Hospital medical college Huazhong University of Science and Technology

    Wuhan, Hubei

    Guohui Cui, M.D.

    Recruiting

  • Henan Provincial Oncology Hospital

    Zhenzhou, Henan

    Keshu Zhou, Doctor

    Recruiting

Other trials in China

About this study

Official title: A Phase Ib/II Study of the Safety, Pharmacokinetic, Pharmacodynamic and Efficacy of APG-2575 Single Agent and in Combination With Other Therapeutic Agents in Patients With Relapsed/Refractory CLL/SLL

The purpose of this study is to assess the safety, pharmacokinetic, pharmacodynamic and efficacy of APG-2575 single agent and in combination with other therapeutic agents in patients with relapsed/refractory CLL/SLL.

Read the detailed description

This is an open-label, multi-center Phase Ib/II study of safety, PK, PD and efficacy of APG-2575 as a single agent or in combination with rituximab or ibrutinib in relapsed/refractory CLL/SLL patients.

This study consists of two parts: The first part is the APG-2575 single agent cohort expansion. The cohort expansion will be conducted at three dose levels of 400 mg, 600 mg, and 800 mg. And up to 15 patients are planned to be enrolled at each dose level.

The second part contains two arms: APG-2575 combined with rituximab (Arm A) and APG-2575 combined with ibrutinib (Arm B). Both the two arms consist of two stages: dose escalation stage (first stage) and dose expansion stage (second stage). The first stage is the study of APG-2575 dose escalation combined with rituximab/ibrutinib. APG-2575 dose escalates according to the standard 3+3 design, the initial dose is 200mg, the dose of APG-2575 will be increased in subsequent levels, to 400mg, 600mg, 800mg respectively. The second stage is the MTD/RP2D expansion stage. Once the respective MTD/RP2D of arms A and B is determined, up to 15 subjects in each MTD/RP2D dose level would be enrolled.

APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycle.

Rituximab, on cycle 1 day 8(C1D8): 375mg/m2; on cycles 2-6 day l(C2-6D1): 500mg/m2, a total of six infusions.

Ibrutinib 420 mg will be orally administered daily beginning from cycle 1 day 8 and continuously thereafter, every 4 weeks as a cycle.

Being tested
APG-2575, Rituximab, Ibrutinib
Keywords
APG-2575, rituximab, ibrutinib, chronic lymphocytic leukemia(CLL), small lymphocytic lymphoma(SLL)
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • APG-2575Drug

    APG-2575 orally once daily, every 28 days as a cycle.

  • RituximabDrug

    Rituximab 375mg/m2 ivgtt on C1D8 and 500mg/m2 ivgtt on C2-6D1.

  • IbrutinibDrug

    Ibrutinib 420mg orally once daily during C1D8-28 and following cycles.

Study groups in NCT04494503
Study groupRoleWhat they receive
APG-2575 single agent in Relapse/Refractory CLL/SLLExperimentalAPG-2575 orally once daily at 400mg, 600mg, 800mg dose levels respectively, every 28 days as a cycle.
Receives: Drug: APG-2575
APG-2575+Rituximab in Relapse/Refractory CLL/SLLExperimentalStage 1:APG-2575 orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg. Rituximab 375mg/m2 ivgtt on C1D8 and 500mg/m2 ivgtt on C2-6D1. Every 28 days as a cycle. Stage 2: APG-2575 MTD/RP2D combined with rituximab. Every 28 days as a cycle.
Receives: Drug: APG-2575; Drug: Rituximab
APG-2575+ibrutinib in Relapse/Refractory CLL/SLLExperimentalStage 1: APG-2575 orally once daily starting from 200mg and will be increased in subsequent cohorts to 400mg, 600mg, 800mg.Ibrutinib 420mg orally once daily during C1D8-28 and following cycles. Every 28 days as a cycle. Stage 2: APG-2575 MTD/RP2D combined with ibrutinib. Every 28 days as a cycle.
Receives: Drug: APG-2575; Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events of APG-2575 single agent

    Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.

    Measured: Up to 6 cycles (each cycle is 28 days).

  2. Objective Response Rate (ORR) of APG-2575 single agent

    ORR is defined by CR+ CRi + PR(according to NCI-WG CLL(2008)) and by CR+PR ( according to NHL Cheson (2007)).Response will be evaluated every 2 cycles (8 weeks) till complete 6 cycles treatment or one month after last dose.

    Measured: Up to 6 cycles (each cycle is 28 days).

  3. Dose Limiting Toxicities (DLT) of combination therapy

    DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.

    Measured: 28 days.

  4. Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)

    MTD/RP2D will be determined based on DLTs observed during cycle one.

    Measured: 28 days.

Secondary outcomes (5)

  1. Maximum plasma concentration (Cmax)

    Cmax of APG-2575 will be assessed in the patients in single agent or combo study. Cmax of ibrutinib will be assessed in the patients treated with APG-2575 combination with ibrutinib.

    Measured: 28 days.

  2. Area under the plasma concentration versus time curve (AUC)

    AUC of APG-2575 will be assessed in the patients in single agent or combo study. AUC of ibrutinib will be assessed in the patients treated with APG-2575 combination with ibrutinib.

    Measured: 28 days.

  3. Objective Response Rate (ORR) of APG-2575 combination therapy

    ORR is defined by CR+ CRi + PR(according to NCI-WG CLL(2008)) and by CR+PR ( according to NHL Cheson (2007)).Response will be evaluated every 2 cycles (8 weeks) till complete 6 cycles treatment or one month after last dose.

    Measured: Up to 6 cycles (each cycle is 28 days).

  4. Minimal residual lesions (MRD) of peripheral blood and/or bone marrow.

    Measured: 2 years.

  5. Survival benefit (PFS) of APG-2575 combination therapy

    PFS,Time from the beginning of treatment to the first occurrence of Progressive Disease (PD) or death.

    Measured: 2 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2020
  2. Study start31 Aug 2020
  3. Primary completion20 Oct 2024
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
123 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04494503
Sponsor's protocol ID
APG2575CC101
Status last verified
Apr 2025
First submitted
21 Jul 2020
Last updated
16 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APG-2575, Rituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Ascentage Pharma Group Inc. at 18 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jianyong Li, M.D. (+86-25-83781120, lijianyonglm@medmail.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events of APG-2575 single agent (time frame: Up to 6 cycles (each cycle is 28 days).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04494503.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2025.

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