A Phase Ib Study of APG-115 Single Agent or in Combination With Azacitidine or Cytarabine in Patients With AML and MDS.
This study tests a new drug called APG-115, either alone or combined with other chemotherapy drugs, in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). These are blood cancers where abnormal cells grow too quickly in the bone marrow. The research aims to find safe and effective doses of this treatment.
Key Objective:This trial is testing whether APG-115 can help stop cancer cell growth by working through a new mechanism, potentially offering a more effective treatment option for patients with AML and MDS.
Who to Consider:Patients with newly diagnosed or previously treated AML or MDS who have exhausted standard treatment options or are not eligible for conventional chemotherapy should consider enrolling.
Trial Parameters
Eligibility Fast-Check
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Brief 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).
Eligibility Criteria
Inclusion Criteria: 1. 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 (score≥4.5) according to IPSS-R risk stratification 2. Age \>/= 18 years. 3. Adequate organ function 4. Subject must have a projected life expectancy of at least 12 weeks. 5. ECOG performance status of 0-1. 6. 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. 7. Subject has a white blood cell count\< 50 × 109/L. Note: Hydroxyurea is permitted to meet this criterion. Exclusion Criteria: 1. Subject has acute promyelocytic leukemia. 2. Patients must not have had leukemia biotherapy 4 weeks prior to starting investigational drug, or less than 5 half-lives small molecular targeted drug therapy, or 28 days any