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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04215809




Registration number
NCT04215809
Ethics application status
Date submitted
30/12/2019
Date registered
2/01/2020
Date last updated
7/02/2024

Titles & IDs
Public title
Study of APG-2575 as a Single Agent or in Combination With Other Therapeutic Agents for CLL/SLL
Scientific title
APG-2575CU101, A Phase Ib Study of APG-2575 as a Single Agent or in Combination With Other Therapeutic Agents in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL
Secondary ID [1] 0 0
APG2575CU101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CLL/SLL 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APG2575

Experimental: APG2575 200mg - APG2575 200mg ramp up

Experimental: APG2575 400mg - APG2575 400mg ramp up

Experimental: APG 2575 600mg - APG2575 600mg ramp up

Experimental: APG2575 800mg - APG2575 800mg ramp up

Experimental: APG2575 1000 mg - APG2575 1000 mg ramp up

Experimental: APG2575 1200mg - APG2575 1200mg ramp up


Treatment: Drugs: APG2575
APG2575 investigation drug in ramp up dosing
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Toxicity Endpoint: dose limiting toxicity (DLT)
Timepoint [1] 0 0
42 days
Primary outcome [2] 0 0
Maximally tolerated dose (MTD)
Timepoint [2] 0 0
42 days

Eligibility
Key inclusion criteria
* 1. =18 years of age. 2. Histologically confirmed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) according to the 2018 international workshop (IW) CLL criteria who must have relapsed or be refractory to at least one prior therapy for CLL/SLL and require treatment by 2018 IWCLL criteria.

3. ECOG) =2. 4. Patient must have objectively documented evidence of disease progression prior to study entry such as: escalating lymphocytes count with an increase > 50% over a period of two months or doubling time in less than 6 months; enlarging adenopathy or splenomegaly; increasing cytopenias; clinical B symptoms -night sweats, fatigue, > 1% weight loss in 6 months, fevers > 100.50F for = one month without infection.

5. In Part 1 of the APG-2575 monotherapy dose escalation portion, patients eligible for dose expansion at doses lower than MTD will have received = 3 prior systemic lines of therapy.

6. Adequate bone marrow function independent of growth factor:
1. Absolute neutrophil count (ANC)=1.0× 109/L in patient without bone marrow involvement. This criterion does not apply to patients with bone marrow involvement by CLL/SLL.
2. Platelets count =30 x 109/L (entry platelet count must be independent of transfusion within 7 days of first dose of study drug).

7. Adequate renal and hepatic function as indicated by:

a. Serum creatinine =1.5×upper limit of normal (ULN); if serum creatinine is >1.5×ULN, creatinine clearance must be = 50 mL/min, calculated using the Cockcroft and Gault formula(140-Age)x mas (kg)/(72x creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976) b. Total bilirubin =1.5 x ULN, except patients with known Gilbert's syndrome. c. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2.5 x ULN, Alkaline phosphatase<2.5×ULN d. International normalized Ratio (INR), Prothrombin Time (PT) or Activated Partial Thromboplastin time (APTT)=1.5×ULN unless the patient is receiving anticoagulant therapy as long as PT or APTT is within therapeutic range of intended use of anticoagulants.

8. Females of childbearing potential (i.e. not postmenopausal for at least 2 years or surgically sterile) must have negative results for pregnancy test performed:

a. At Screening on a serum sample obtained within 14 days prior to the first study drug administration b. Prior to dosing on a urine sample obtained on the first day of study drug administration, if it has been>7 days since obtaining the serum pregnancy test results.

9. Females of childbearing potential and non-sterile males must practice at least one of the following methods of birth control with partner(s) throughout the study and for 90 days after discontinuing study drug:
1. Total abstinence from sexual intercourse as the preferred lifestyle of the patient; periodic abstinence is not acceptable;
2. Surgically sterile partner(s); acceptable sterility surgeries are: vasectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy;
3. Intrauterine device (IUD);
4. Double-barrier method (contraceptive sponge, diaphragm or cervical cap with spermicidal fellies or cream AND a condom);
5. Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 3 months prior to study drug administration.

If hormonal contraceptives are used, the specific contraceptive must have been used for at least 3 months prior to study drug administration.

10. Male patients must refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug.

11. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures).

12. Willingness and ability to comply with study procedures and follow-up examination.
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 1. Patient has undergone allogeneic stem cell transplant < 90 days 2. Patient has active graft-versus-host disease or require immunosuppressive therapy.

3. Richter's Syndrome. 4. Prior anti-Bcl-2 treatment (except patients who discontinued treatment for reasons other than disease progression) 5. For combination cohorts:
1. In the acalabrutinib and APG-2575 cohort, patients who are on anticoagulants or patients that discontinued due to acalabrutinib toxicity (Note: Patients who received a BTK inhibitor therapy may participate whether, or not, they progressed following BTK inhibitor treatment).
2. Prior CDK-9 inhibitor in the voruciclib plus APG-2575 cohort 6. Known human immunodeficiency virus syndrome (HIV) infection 7. Known active hepatitis B infection, as defined seropositivity for Hep B surface antigen (HBsAg) or known hepatitis C infection as determined by hepatitis C antibody with elevated liver enzymes as defined in the inclusion criteria or any other evidence of active hepatitis C such as currently on treatment 8. Has known central nervous system (CNS) involvement. 9. Prior malignancy that required treatment and has shown recurrence within 2 years of screening (except for non-melanoma skin cancer or adequately treated carcinoma in situ of cervix or breast). Cancer treated within 2 years with curative intent and without recurrence as well as prostate cancer on active surveillance are allowed.

10. Concurrent treatment with an investigational agent, received biologics (=28 days), or small molecule targeted therapies (=5 half-life) or other anti-cancer therapies (including chemotherapy) =14 days of first dose of study drug 11. Patient is pregnant or breast feeding 12. Has received the following within 7 days prior to the first dose of study drug:

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1. Steroid therapy at a dose greater than prednisone 20 mg daily (or equivalent) for anti-neoplastic intent;
2. CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin;
3. Potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort; 13. Radiation within 14 days of study entry 14. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that have not recovered to = grade 1 or baseline, except alopecia or neuropathy.

15. Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patient with active wound healing, patients who have had major surgery within 28 days from 1st dose of study drug 16. Has a cardiovascular disability status of New York Heart Association Class = 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea or anginal pain.

17. Unstable angina or myocardial infarction within 3 months of enrollment 18. QTc interval> 480ms (Bazett or Fredericia formulae) or other remarkable abnormal ECG findings, including second-degree type II atrioventricular block, third-degree atrioventricular block or bradycardia (ventricular rate of less than 50 beats per minute).

19. Has gastrointestinal conditions that could affect the absorption of APG-2575 in the opinion of the Investigator.

20. Uncontrolled concurrent illness including, but not limited to: uncontrolled diabetes mellitus, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements.

21. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
35
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Princess Alexandria Hospital - Brisbane
Recruitment hospital [2] 0 0
Frankston Private Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
QLD 4102 - Brisbane
Recruitment postcode(s) [2] 0 0
3199 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Ascentage Pharma Group Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Assess the safety and tolerability, identify dose-limiting toxicities (DLT) and determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of APG-2575.
Trial website
https://clinicaltrials.gov/study/NCT04215809
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Yifan Zhai, MD, PhD
Address 0 0
Ascentage Pharma Group Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Laura Glass
Address 0 0
Country 0 0
Phone 0 0
301-520-5964
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04215809