Hematologic Malignancies
Conditions
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.
Detailed description
APG-2575 will be administered orally, once daily for consecutive 4 weeks as one cycles. Initially, the start dose is 20mg. Single patient cohorts will be evaluated, the dose of APG-2575 will be increased in subsequent cohorts, to 50 mg, 100 mg, 200 mg, 400 mg, 600mg and 800mg accordingly. If there is any one of the following event is observed, a DLT, two drug related Grade 2 toxicities or one drug related ≥ Grade 3 toxicity, or laboratory or clinical TLS, or suspected hypersensitivity reaction occur in Cycle 1, or dose level of 400 mg is reached, the dose escalation will convert to the standard 3+3 design, If ≥ 2/6 patients develop DLT at any dose level dose escalation will cease and the dose level immediately below will be expanded to 6 patients. If ≤ 1/6 patients develop a DLT at the highest dose reached this will be declared the MTD. After the MTD is defined, a maximum of 20 patients will be treated at that dose level.
Interventions
DRUGAPG-2575
APG-2575 will be administered as an oral tablet
Sponsors
Ascentage Pharma Group Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
dose escalation and dose expansion after MTD
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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:
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 28 days | Patients with APG-2575 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) | 28 days | Maximum plasma concentration (Cmax) will be assessed in the patients treated with APG-2575 |
| Area under the plasma concentration versus time curve (AUC) | 28 days | Area under the plasma concentration versus time curve (AUC) of APG-2575 will be assessed in the patients treated with APG-2575 |
| Anti-tumor effects of APG-2575 | up to 2 years | Response will be evaluated every 2 cycles (8 weeks), by the investigator based on disease specific criteria. |
Countries
Australia, United States
Contacts
Primary ContactLaura Glass
Outcome results
None listed