Chronic Lymphocytic Leukemia, Non-hodgkin Lymphoma, Small Lymphocytic Lymphoma
Conditions
Brief summary
ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies \[Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other NHL subtypes).
Detailed description
The ZX-101A-101 study will consist of 2 parts: * Part 1: ZX-101A Dose Escalation * Part 2: ZX-101A Dose Expansion The Part 1 (dose escalation) of the study is designed to determine the safety and tolerability of ZX-101A administered orally once daily in 28-day cycles. The Part 2 (dose expansion) of the study is designed to further investigate the safety, tolerability, pharmacokinetics and pharmacodynamic and clinical activities of ZX-101A administered orally once daily in 28-day cycles at the selected recommended Phase 2 dose (RP2D). Results of clinical findings in patients in the dose-escalation portion of the study will be reviewed to identify conditions (or genetic characteristics) most likely to respond to ZX-101A. These select types of hematologic malignancies will be enrolled in cohorts in the dose-expansion part of the study. Male or female patients who are 18 years of age or older with relapsed/resistant or refractory advanced hematologic malignancies (CLL/SLL, iNHL, and other NHL subtypes) will be included in the study provided that all inclusion and exclusion criteria are satisfied. Up to three cohorts are planned in Part 2 - Dose Expansion of the study: 1) relapsed/resistant or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), 2) relapsed/resistant or refractory indolent Non- Hodgkin's Lymphoma (iNHL), and based on emerging data from Part 1-Dose Expansion, a third cohort consisting of other types of NHL may be included.
Interventions
DRUGZX-101A
Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
Sponsors
Hangzhou Zenshine Pharmaceuticals Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females who are ≥ 18 years old * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. * Failed at least 2 prior systemic standard therapies. * Histopathological confirmed diagnosis of CLL/SLL, indolent NHL,and other NHL subtypes. * Documented active disease that is relapsed/resistant or refractory requiring treatment after established therapy shown to have clinical benefit. * Acceptable bone marrow, kidney, and liver function. * No transfusion or cytokine support for ≥ 2 weeks before initiating study treatment. * Ability to swallow and retain oral medications (see
Exclusion criteria
#20 below). * Negative serum pregnancy test in women of childbearing potential at Screening. * Women of childbearing potential and men who partner with a woman of childbearing potential must agree to use effective contraceptive methods. * Men must agree to no sperm donations during the study and for 3 months after the last dose of ZX-101A. * Understands the requirements of the study (e.g. periodic imaging studies, periodic blood sampling, bone marrow studies), is willing to comply with all study procedures and signed the Institutional Review Board (IRB)-approved informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Defining the recommended Phase 2 dose (RP2D) of ZX-101A. | From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days. | To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1. |
| Safety and tolerability of ZX-101A | From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days. | To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Half-life of ZX-101A | Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5 | To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A |
| Phospho-AKT (p-AKT) levels in whole blood | Days 1 and 2 of Cycle 1 (each cycle is 28 days) | To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A. |
| Objective response rate (ORR) | Up to 2 years | To evaluate the objective response rate (ORR) as determined by the specific disease response criteria |
| Peak Plasma Concentration of ZX-101A | Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5 | To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A |
| Progression free survival (PFS) | Up to 2 years | To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause |
| Overall survival (OS) | Up to 2 years | To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause |
| Duration of response (DoR) | Up to 2 years | To examine the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause |
| Area under the plasma concentration of ZX-101A | Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5 | To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A |
Countries
United States
Outcome results
None listed