Acute Myeloid Leukemia, Non Hodgkin Lymphoma
Conditions
Keywords
BCL-2 Inhibitors, BH3 mimetics
Brief summary
Phase 1 dose escalation study of ZN-d5 in subjects with relapsed or refractory non-Hodgkin lymphoma (NHL) or acute myeloid leukemia (AML).
Detailed description
This is an open-label multicenter Phase 1 dose escalation study evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2 inhibitor ZN-d5 in subjects with (NHL) or (AML) in order to determine the recommended phase 2 dose of ZN-d5.
Interventions
DRUGZN-d5
Oral agent; 25 mg or 100 mg formulation
Sponsors
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: NHL: relapsed or refractory NHL including DLBCL, FL, MZL, MCL, LCL, LPL and PTC * Subjects must have received at least 2 prior lines of therapy and have either failed or not be eligible for any available therapies expected to provide clinical benefit and have measurable disease. AML: Primary, secondary, or treatment-related AML, relapsed or refractory to prior therapy, which may include failure of one cycle of induction therapy. * White blood cell count \< 25 × 109/L. Cytoreduction prior to treatment is acceptable. * Subjects may not be pregnant and must agree to use an effective method of contraception. * Eastern Cooperative Oncology Group performance status ≤ 2. * Estimated life expectancy of at least 12 weeks. * Adequate hematologic and organ function, including creatinine clearance ≥ 60 mL/min. Key
Exclusion criteria
* Recent interventions including major surgery, radiation therapy, stem cell transplant. * Treatment with anti-neoplastic agents with 5 half-lives. * Significant unresolved toxicity from prior treatments including active GVHD. * Active central nervous system disease. * Clinically substantial myocardial impairment. * Prior therapy with venetoclax.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Dose Limiting Toxicities | Through completion of Cycle 1; 1 to 2 months. | Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects. |
| Incidence and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0 | Through study completion, typically < 12 months | Safety profile of ZN-d5. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameters for ZN-d5 - AUC | approximately 6 months | Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using area under the plasma concentration versus time curve (AUC). |
| For NHL, evaluate response according to the Lugano 2014 classification | Through study completion, typically < 12 months | Evaluate response according to the Lugano 2014 classification for NHL subjects. The Lugano Classification is based on a 5-point scale for scoring of metabolically active lesions detected by PET-CT in FDG-avid lymphomas, and lesion size for non-FDG-avid tumors. A complete metabolic response would require a score of 1 or 2 on target and non-target lesions and the spleen for high-risk disease, and a score of 1,2, or 3 for low-risk disease. A partial response, no response, or progression would require a score of 4 or 5 for low-risk disease, and a score of 3, 4, or 5 for high-risk disease. |
| Pharmacokinetic parameters for ZN-d5 - Cmax | approximately 6 months | Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using peak plasma concentration (Cmax). |
| For AML, duration of remission based on European LeukemiaNet 2017 criteria | Through study completion, typically < 12 months | Evaluate duration of remission according to the European LeukemiaNet 2017 criteria. |
| For AML, remission rate based on European LeukemiaNet 2017 criteria | Through study completion, typically < 12 months | Evaluate remission rate according to the European LeukemiaNet 2017 criteria (Overall Response Rate (ORR) defined as Complete Remission (CR) + CR with incomplete hematologic recovery (CRi) + Morphologic Leukemia-Free State (MLFS) + Partial Remission (PR)) for AML subjects. |
| Pharmacokinetic parameters for ZN-d5 - Tmax | approximately 6 months | Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using the time to maximum plasma concentration (Tmax). |
Countries
Australia, Bulgaria, Croatia, Poland, South Korea, Spain, Ukraine
Outcome results
None listed