Clinical trial NCT04500587: Phase 1 First in Human Study of ZN-d5 as a Single Agent
Official title: Phase 1 First in Human Dose-Escalation Study of ZN-d5 as a Single Agent in Subjects With Non-Hodgkin Lymphoma or Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Non Hodgkin Lymphoma
Keywords: BCL-2 Inhibitors
BH3 mimetics
Lead sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-08-05
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Observed Dose Limiting Toxicities
timeFrame: Through completion of Cycle 1; 1 to 2 months.
measure: Incidence and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0
timeFrame: Through study completion, typically < 12 months
Secondary outcomes:
measure: Pharmacokinetic parameters for ZN-d5 - Cmax
timeFrame: approximately 6 months
measure: Pharmacokinetic parameters for ZN-d5 - Tmax
timeFrame: approximately 6 months
measure: Pharmacokinetic parameters for ZN-d5 - AUC
timeFrame: approximately 6 months
measure: For NHL, evaluate response according to the Lugano 2014 classification
timeFrame: Through study completion, typically < 12 months
measure: For AML, remission rate based on European LeukemiaNet 2017 criteria
timeFrame: Through study completion, typically < 12 months
measure: For AML, duration of remission based on European LeukemiaNet 2017 criteria
timeFrame: Through study completion, typically < 12 months
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: Site 2708
state: New South Wales
city: Liverpool
country: Australia
facility: Site 2704
state: New South Wales
city: Kurralta Park
country: Australia
facility: Site 2710
state: South Australia
city: Hobart
country: Australia
facility: Site 2709
state: Tasmania
city: Sofia
country: Bulgaria
facility: Site 1202
city: Varna
country: Bulgaria
facility: Site 1201
city: Zagreb
country: Croatia
facility: Site 3201
city: Pusan
country: Korea, Republic of
facility: Site 2901
city: Seoul
country: Korea, Republic of
facility: Site 2903
city: Gdansk
country: Poland
facility: Site 2403
city: Barcelona
country: Spain
facility: Site 3001
city: Bilbao
country: Spain
facility: Site 3005
city: Valencia
country: Spain
facility: Site 3003
city: Kiev
country: Ukraine
facility: Site 2001
Study officials:
affiliation: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
name: K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals
role: STUDY_DIRECTOR
References: