T-Prolymphocytic Leukemia, Non-Hodgkins Lymphoma
Conditions
Brief summary
The goal of this study is to evaluate the pharmacokinetics (PK), safety, and efficacy of APG-115 as a single agent or in combination with APG-2575 in patients with T-PLL and NHL.
Detailed description
This is a phase IIa, open-label, multi-center, clinical trial of interfering the binding of MDM2 oncoprotein with the tumor suppressor P53 protein, leads to increased P53 and P21 protein expression and activates P53-mediated apoptosis. The hypothesis is that APG-115 monotherapy and in combination with APG-2575 will shows good safety and efficacy in patients with R/R T-PLL and NHL
Interventions
Sponsors
Ascentage Pharma Group Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study consists of Part 1 APG-115 as monotherapy. Part 2 APG-2575 in combination with APG-115 dose escalation and APG-2575 in combination with APG-115 dose expansion phase. APG-115 and APG-2575 will be orally administrated on 21-day cycles. Patients will receive APG-115 QOD, 2 weeks on, 1 week off, and APG-2575 QD, in repeated 21-day cycles.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years old 2. Patients with relapsed/refractory T-PLL who have active disease and have received at least one prior therapy; Patients with histologically confirmed diagnosis of NHL, NHL Patients must be either relapsed, refractory, intolerant, or are considered ineligible for therapies known to provide clinical benefit; 3. Patients must not have had chemotherapy or antibody therapy for 7 days prior to starting APG-115 and/or APG-2575. However, patients with rapidly proliferative disease may receive hydroxyurea or decadron until 24 hours prior to starting therapy on this protocol. 4. Absolute neutrophil count (ANC) ≥ 500/mm˄3; hemoglobin ≥ 60 g/L; platelet count ≥ 30,000/mm˄3 5. Patients with adequate organ function; 6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; 7. 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/her legally authorized representative is required prior to their enrollment on the protocol.
Exclusion criteria
1. Patient previously treated with a murine double minute 2 (MDM2) inhibitor. 2. Known active, uncontrolled central nervous system (CNS) malignancy 3. Patients require graft versus host therapy, or require continued treatment with systemic immunosuppressive agents (calcineurin inhibitors within 4 weeks prior to the first dose of study drug). 4. Patients who have any conditions or illness that, according to the opinions of the Investigators or the medical monitor, would compromise patient safety or interfere with the evaluation of safety and efficacy to the study drug(s). 5. Patients who have used strong CYP2C8 inhibitors, or moderate or strong CYP3A4 inhibitors or inducers within washout period of 14 days or 7 half-lives before the first administration of study drugs, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose of APG-115 | 21 days | To evaluate the safety of APG-115 as a single agent |
| Maximum tolerated dose of APG-115+APG-2575 | 21 days | To evaluate the maximum tolerated dose of APG-115 and APG-2575 in combination |
Countries
United States
Contacts
Primary ContactGenevieve Frank
Backup ContactJocelyn Budzynski
Outcome results
None listed