Acute Myeloid LeukemiaPhase 1NCT04500587
Phase 1 First in Human Study of ZN-d5 as a Single Agent
A Phase 1 study testing ZN-d5 in people with Acute Myeloid Leukemia and Non Hodgkin Lymphoma, run by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. at 14 sites in 7 countries.
Trial summary
Phase 1 dose escalation study of ZN-d5 in subjects with relapsed or refractory non-Hodgkin lymphoma (NHL) or acute myeloid leukemia (AML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Non Hodgkin Lymphoma
- What is being tested?
- ZN-d5
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 14 sitesin 7 countries
- Study dates
- 13 Oct 2020to 12 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
14 sites in 7 countries.
14 sites in 7 countries
Australia4 sites
Site 2708
Darlinghurst, New South Wales
Site 2709
Hobart, Tasmania
Site 2710
Kurralta Park, South Australia
Site 2704
Liverpool, New South Wales
About this study
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
Phase 1 dose escalation study of ZN-d5 in subjects with relapsed or refractory non-Hodgkin lymphoma (NHL) or acute myeloid leukemia (AML).
Read the 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.
- Conditions
- Acute Myeloid Leukemia, Non Hodgkin Lymphoma
- Being tested
- ZN-d5
- Keywords
- BCL-2 Inhibitors, BH3 mimetics
- Medical subject headings
- Leukemia, Myeloid, Acute, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZN-d5Drug
Also called Study Drug
Oral agent; 25 mg or 100 mg formulation
| Study group | Role | What they receive |
|---|---|---|
| ZN-d5 Single Agent Dose Escalation - NHL | Experimental | Non-Hodgkin Lymphoma Receives: Drug: ZN-d5 |
| ZN-d5 Single Agent Dose Escalation - AML | Experimental | Acute Myeloid Leukemia Receives: Drug: ZN-d5 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Observed Dose Limiting Toxicities
Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.
Measured: Through completion of Cycle 1; 1 to 2 months.
Incidence and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0
Safety profile of ZN-d5.
Measured: Through study completion, typically < 12 months
Secondary outcomes (6)
Pharmacokinetic parameters for ZN-d5 - Cmax
Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using peak plasma concentration (Cmax).
Measured: approximately 6 months
Pharmacokinetic parameters for ZN-d5 - Tmax
Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using the time to maximum plasma concentration (Tmax).
Measured: approximately 6 months
Pharmacokinetic parameters for ZN-d5 - AUC
Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using area under the plasma concentration versus time curve (AUC).
Measured: approximately 6 months
For NHL, evaluate response according to the Lugano 2014 classification
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.
Measured: Through study completion, typically < 12 months
For AML, remission rate based on European LeukemiaNet 2017 criteria
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.
Measured: Through study completion, typically < 12 months
For AML, duration of remission based on European LeukemiaNet 2017 criteria
Evaluate duration of remission according to the European LeukemiaNet 2017 criteria.
Measured: Through study completion, typically < 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2020
- Study start13 Oct 2020
- Primary completion12 Dec 2023
- Study completion12 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals, Study director, K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04500587
- Sponsor's protocol ID
- ZN-d5-001
- Status last verified
- Sep 2024
- First submitted
- 30 Jul 2020
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04500587
- Acronym / sponsor ID
- ZN-d5-001
- Conditions
- Acute Myeloid Leukemia, Non Hodgkin Lymphoma
- Keywords
- BCL-2 Inhibitors, BH3 mimetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Oct 2020 (actual)
- Primary completion
- 12 Dec 2023 (actual)
- Study completion
- 12 Dec 2023 (actual)
- First posted
- 5 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZN-d5 Single Agent Dose Escalation - NHL | Experimental | Drug: ZN-d5Non-Hodgkin Lymphoma |
| ZN-d5 Single Agent Dose Escalation - AML | Experimental | Drug: ZN-d5Acute Myeloid Leukemia |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZN-d5Also: Study DrugOral agent; 25 mg or 100 mg formulation | Drug | ZN-d5 Single Agent Dose Escalation - AML, ZN-d5 Single Agent Dose Escalation - NHL |
Primary outcome
Observed Dose Limiting Toxicities
Time frame: 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
Time frame: Through study completion, typically < 12 months
Safety profile of ZN-d5.
6 secondary outcomes
Pharmacokinetic parameters for ZN-d5 - Cmax
Time frame: approximately 6 months
Pharmacokinetic parameters for ZN-d5 - Tmax
Time frame: approximately 6 months
Pharmacokinetic parameters for ZN-d5 - AUC
Time frame: approximately 6 months
For NHL, evaluate response according to the Lugano 2014 classification
Time frame: Through study completion, typically < 12 months
For AML, remission rate based on European LeukemiaNet 2017 criteria
Time frame: Through study completion, typically < 12 months
For AML, duration of remission based on European LeukemiaNet 2017 criteria
Time frame: Through study completion, typically < 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals study director
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
14 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZN-d5 in people with Acute Myeloid Leukemia and Non Hodgkin Lymphoma, run by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. at 14 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Australia, Spain, Bulgaria, South Korea, Croatia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Observed Dose Limiting Toxicities (time frame: Through completion of Cycle 1; 1 to 2 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.