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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03537482




Registration number
NCT03537482
Ethics application status
Date submitted
27/03/2018
Date registered
25/05/2018
Date last updated
30/03/2020

Titles & IDs
Public title
APG-2575 Study of Safety, Tolerability ,PK/PD in Patients With Hematologic Malignancies
Scientific title
A Phase I Study of Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Property of Orally Administered APG-2575 in Patients With Hematologic Malignancies
Secondary ID [1] 0 0
APG2575-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematologic Malignancies 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APG-2575

Experimental: single-agent, open-label, Phase I study of APG-2575 - The study consists of the dose escalation stage and the dose expansion stage


Treatment: Drugs: APG-2575
APG-2575 will be administered as an oral tablet

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) - Patients with APG-2575 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0
Timepoint [1] 0 0
28 days
Secondary outcome [1] 0 0
Maximum plasma concentration (Cmax) - Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-2575
Timepoint [1] 0 0
28 days
Secondary outcome [2] 0 0
Area under the plasma concentration versus time curve (AUC) - Area under the plasma concentration versus time curve (AUC) of APG-2575 will be assessed in the patients treated with APG-2575
Timepoint [2] 0 0
28 days
Secondary outcome [3] 0 0
Anti-tumor effects of APG-2575 - Response will be evaluated every 2 cycles (8 weeks), by the investigator based on disease specific criteria.
Timepoint [3] 0 0
up to 2 years

Eligibility
Key inclusion criteria
1. Age =18 years old.

2. Histologically confirmed diagnosis of either one of the B-cell hematologic
malignancies including multiple myeloma, chronic lymphocytic leukemia,
lymphoplasmacytic lymphoma, and non-Hodgkin's lymphoma such as mantle cell lymphoma,
diffuse large B cell lymphoma, Waldenstrom macroglobulinemia (WM) and acute myeloid
leukemia

3. Patient must have relapsed or refractory to, intolerant to, or are considered
ineligible for therapies known to provide clinical benefit. In addition,

a. AML Patients will be eligible if they have failed standard induction regimen, are
not considered candidate for further chemotherapy or stem cell transplantation or have
primary refractory AML.

4. Life expectancy = 3 months.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1 in dose
escalation ; 0-2 in dose expansion.

6. QTc interval =450ms in males, and =470ms in females.

7. Adequate bone marrow function independent of growth factor:

8. Absolute neutrophil count (ANC) =1.0 X 109/L.

9. Hemoglobin = 8.0 g/dL.

10. Platelets count = 30 X 109/L (entry platelet count must be independent of transfusion
within 7 days of first dose).

11. Adequate renal and liver function as indicated by:
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients who meet any of the following exclusion criteria are not to be enrolled in this
study:

1. Prior history of allogeneic cell transplant.

2. Subjects have been diagnosed with Burkitt's lymphoma, Burkitt-like lymphoma, or
lymphoblastic lymphoma/leukemia.

3. Received chemotherapy within 14 days (42 days for nitrosoureas or mitomycin C) prior
to entering the study.

4. Received biologic (< 28 days), small molecule targeted therapies (< 5 half-life) or
other anti-cancer therapy within 21 days of study entry.

5. Radiation within 14 days of study entry, thoracic radiation within 28 days of study
entry.

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

7. Has known active central nervous system (CNS) involvement.

8. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not
recover to = Grade 1 except alopecia or neuropathy.

9. Concurrent treatment with an investigational agent, 14 days for small molecular agents
and/or 28 days for biologics treatment prior to the first dose of therapy.

10. Failure to recover adequately, as judged by the investigator, from prior surgical
procedures. Patients with active wound healing, 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.

11. Unstable angina, myocardial infarction, or a coronary revascularization procedure
within 180 days of study entry.

12. Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic
infections, or any other disease or condition associated with chronic inflammation.

13. Active infection requiring systemic antibiotic/ antifungal medication, known
clinically active hepatitis B or C infection, or on antiretroviral therapy for HIV
disease.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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
Single group
Other design features
Phase
Phase 0
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St. Vincent Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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
Minnesota
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
Texas

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, single-agent, open-label, Phase I study of APG-2575. The study
consists of the dose escalation stage and the dose expansion stage.
Trial website
https://clinicaltrials.gov/show/NCT03537482
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Yifan Zhai, MD
Address 0 0
Country 0 0
Phone 0 0
2405056608
Fax 0 0
Email 0 0
yzhai@ascentagepharma.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03537482