A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.

  • STATUS
    Recruiting
  • participants needed
    90
  • sponsor
    Ascentage Pharma Group Inc.
Send
Updated on 16 February 2024
See if I qualify
cancer
white blood cell count
myeloid leukemia
cytarabine
acute leukemia
azacitidine
hydroxyurea
leukemia
bone marrow procedure
blood cell count
acute myeloid leukemia

Summary

Acute myeloid leukemia is a malignant disorder characterized by the rapid, uncontrolled proliferation of malignant clonal hematopoietic stem cells that accumulate as immature, undifferentiated cells (blasts) in the bone marrow and circulation.

APG-115 is a potent and orally active small-molecule MDM2 inhibitor, it binds to MDM2 protein and shows potent cell growth inhibitory activity in vitro with low nanomolar potencies in a subset of human cancer cell lines. APG-115 has demonstrated its strong antitumor activities with either daily or less frequent dosing-schedules in the acute leukemia xenograft models.

This is a phase 1b, open-label, three-stages study that will initially evaluate the safety and PK/PD profile of APG-115 as a single agent, followed by a combination of APG-115 + azacytidine or cytarabine in R/R AML or MDS subjects.

Patients will continue treatment for maximally 6 cycles or until progression of disease or unacceptable toxicity is observed or administrative discontinuation whichever occurs first. Patients who continue to be benefit after 6 cycles' treatment will receive additional cycles of treatment until progression of disease, unacceptable toxicity is observed or administrative discontinuation. (As long as it is proven safe).

Description

Stage 1: This will be a 3+3 dose escalation to determine the DLTs and MTD/RP2D of APG-115 given according to the different dose levels once daily from Days 1 to 7 every 28 days.

Stage 2: After stage 1 of APG-115 single agent dose escalation first cycle is completed, stage 2 can be initiated with the combination regimen. This will be a 3+3 dose escalation to determine the MTD/RP2D and DLTs of APG-115 + AZA(arm A)/Cytarabine (arm B)combination.

Stage 3: dose expansion of the combination regimes.

Details
Condition Preleukemia, Acute myeloid leukemia, Acute myeloid leukemia, MYELODYSPLASTIC SYNDROME
Age 18years - 100years
Treatment Azacitidine, Cytarabine, APG-115
Clinical Study IdentifierNCT04275518
SponsorAscentage Pharma Group Inc.
Last Modified on16 February 2024

Eligibility

 Yes No Not Sure

Inclusion Criteria

Patients with a diagnosis of histologically confirmed relapsed or refractory (R/R) acute myeloid leukemia by WHO classification or relapsed/progressed high/very high risk MDS (score4.5) according to IPSS-R risk stratification
Age >/= 18 years
Adequate organ function
Subject must have a projected life expectancy of at least 12 weeks
ECOG performance status of 0-1
Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol
Subject has a white blood cell count< 50 109/L. Note: Hydroxyurea is permitted to meet this criterion

Exclusion Criteria

Subject has acute promyelocytic leukemia
Patients must not have had leukemia biotherapy 12 weeks prior to starting investigational drug, or less than 5 half-lives small molecular targeted drug therapy, or 28 days any anti-cancer therapy (whichever is longer)
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
Active infection requiring systemic antibiotic/antifungal medication, known clinically active hepatitis B or C, or HIV infection
Participants who have received allogeneic HSCT, or autologous HSCT within 12 months
Patients with active, uncontrolled CNS leukemia will not be eligible
Any prior systemic MDM2-p53 inhibitor treatment
Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study
Subject has a history of other malignancies within 5 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
Clear my responses
Read more

How to participate?

Step 1 Connect with a study center
Message sent successfully.
We have submitted the information you provided to the research team at the location you chose. For your records, we have sent a copy of the message to your email address.
If you would like to be informed of other studies that may be of interest to you, you may sign up for Patient Notification Service.
Sign up

Send a message

Enter your contact details to connect with study team

Investigator Avatar

Primary Contact

First name*
Last name*
Email*
Phone number*
Other language

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

cancer
white blood cell count
myeloid leukemia
cytarabine
acute leukemia
azacitidine
hydroxyurea
leukemia
bone marrow procedure
blood cell count
acute myeloid leukemia

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer
Add a private note
  • abc Select a piece of text.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.