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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04964518




Registration number
NCT04964518
Ethics application status
Date submitted
23/06/2021
Date registered
16/07/2021
Date last updated
25/10/2023

Titles & IDs
Public title
A Study of APG-2575 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML)
Scientific title
A Phase Ib/II Study of APG-2575 in Combination With Azacitidine in Patients With Acute Myeloid Leukemia (AML), Mixed Phenotype Acute Leukemia (MPAL), Chronic Myelomonocytic Leukemia (CMML) and Higher-Risk Myelodysplastic Syndrome (MDS
Secondary ID [1] 0 0
APG2575AU101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
AML, Adult 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

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

Experimental: APG2575 + Azacitidine - 200 mg APG2575 dose ramp up +AZA


Treatment: Drugs: APG 2575 ramp up arm
APG2575 ramp up + Azacitidine
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DLT
Timepoint [1] 0 0
28 days

Eligibility
Key inclusion criteria
Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia (AML) or mixed phenotype acute leukemia (MPAL) or Chronic Myelomonocytic Leukemia (CMML) or relapsed/refractory Higher-Risk MDS by 2016 WHO classification for which no available standard therapies are indicated or anticipated to result in a durable response.

* MPAL will include biphenotypic leukemia, bilineal leukemia, undifferentiated leukemia, mixed lineage leukemia, leukemia of ambiguous lineage, T/myeloid leukemia, B/myeloid leukemia, or other diagnosis indicating the presence of multiple lineages within the cell population.
* Relapsed/refractory MDS will be defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy with Overall Revised International Prognostic Scoring System (IPSS-R) score > 3 (intermediate, high or very high).
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant women.
2. Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Have had leukemia therapy within 14 days prior to starting investigational drug.

However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study.
4. Have taken strong inhibitors or inducers of CYP3A4 within 7 days prior to the first dose of APG-2575.
5. Have acute promyelocytic leukemia (French-American-British Class M3 AML or WHO classification APL with PML-RARA) or AML/MPAL with BCR-ABL1 positive.
6. Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection or active COVID-19. (Patients who have received COVID-19 vaccination will be considered as eligible for the study.)
7. Have active/ongoing graft-versus host disease (GVHD) or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose).
8. Myeloablative therapy with autologous or allogeneic hematopoietic stem cell rescue within 6 months of study treatment initiation.
9. Documented hypersensitivity to any of the components of the therapy program.
10. Active, uncontrolled CNS leukemia.
11. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use at least 1 form of barrier birth control (such as condom) prior to study entry and for the duration of study participation.
12. History of other malignancies within 2 years prior to study entry, with the exception of:

* Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast.
* Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin.
* Previous malignancy confined and surgically resected (or treated with other modalities) with curative intention requires discussion with sponsor.
13. Failure to have recovered (Grade > 1) from prior treatment (including chemotherapy, targeted therapy, immunotherapy, experimental agents, radiation, or surgery), except for alopecia.
14. Unable to swallow tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
15. Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, or corrected QT interval (QTc) =470 msec.
16. 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
Not applicable
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
Other
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
30/07/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/10/2024
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,Western Au
Recruitment hospital [1] 0 0
Pindara Private Hospital - Benowa
Recruitment hospital [2] 0 0
Sunshine Coast University Hospital - Birtinya
Recruitment hospital [3] 0 0
The Northern Hospital - Epping
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
4217 - Benowa
Recruitment postcode(s) [2] 0 0
4575 - Birtinya
Recruitment postcode(s) [3] 0 0
3076 - Epping
Recruitment postcode(s) [4] 0 0
6000 - Perth
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
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
United States of America
State/province [4] 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
This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy and PK of APG-2575 in combination with Azacitidine in the patients with AML/MPAL or MDS/CMML. The study consists of dose escalation (Part I) and dose expansion phase (Part II)
Trial website
https://clinicaltrials.gov/study/NCT04964518
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Qian Niu, MD
Address 0 0
Ascentage Pharma
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Angela Kaiser
Address 0 0
Country 0 0
Phone 0 0
301-509-0357
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/NCT04964518