Acute Myeloid Leukemia (AML)Phase 1/2NCT05682170
Study of the ZN-d5 and ZN-c3 in Subjects With Acute Myeloid Leukemia (AML)
A Phase 1/2 study testing ZN-d5 ZN-c3 and ZN-c3 in people with Acute Myeloid Leukemia (AML), run by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. at 13 sites in United States.
Trial summary
A Phase 1/2 dose escalation study of BCL-2 Inhibitor ZN-d5 and the Wee1 Inhibitor ZN-c3 in Subjects with 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 (AML)
- What is being tested?
- ZN-d5 ZN-c3 and ZN-c3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 13 sitesUnited States
- Study dates
- 1 Dec 2022to 26 Jul 2024
- Phase
- Phase 1/2
- 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
- Adults with AML (including secondary or therapy-related), relapsed from or refractory to one or more prior lines of therapy, which may include venetoclax except in Expansion Cohort A
- ECOG performance status score ≤2.
- Projected life expectancy of at least 12 weeks.
- Estimated glomerular filtration rate ≥60 mL/min
- Women of childbearing potential must not be pregnant and must use effective birth control during the study and for 6 months after the last dose of study drugs.
- Men must agree to use a condom when having intercourse during the study and for 3 months after the last dose of study drugs.
Who cannot join
- Known active CNS involvement
- Diagnosis of acute promyelocytic leukemia.
- Peripheral blast count of >25 × 109/L (cytoreduction permitted).
- Adequate washout from prior therapy including hematopoietic stem cell transplant and recovery from prior treatment-related toxicities to Grade 2 or lower
- Significant cardiovascular disease
- Corrected QT interval (QTc) of >480 msec
- Active hepatitis B or hepatitis C infection
- Concurrent treatment with strong CYP3A inhibitors or strong or moderate CYP3A inducers
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 53792
Tristar Bone Marrow Transplant
Nashville, Tennessee, 37203
NYU Langone Health
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Oregon Health and Science University
Portland, Oregon, 97239
University of California San Francisco
San Francisco, California, 94110
Albert Einstein College of Medicine - Montefiore Medical Center
The Bronx, New York, 10467
About this study
Official title: A Phase 1/2 Dose Escalation Study of the BCL-2 Inhibitor ZN-d5 and the WEE1 Inhibitor ZN-c3 in Subjects With Acute Myeloid Leukemia
A Phase 1/2 dose escalation study of BCL-2 Inhibitor ZN-d5 and the Wee1 Inhibitor ZN-c3 in Subjects with Acute Myeloid Leukemia (AML).
Read the detailed description
This is an open-label multicenter Phase 1/2 dose escalation study, evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2 inhibitor ZN-d5 and Wee1 inhibitor ZN-c3 in subjects with AML.
- Conditions
- Acute Myeloid Leukemia (AML)
- Being tested
- ZN-d5 ZN-c3, ZN-c3
- Keywords
- BCL-2 Inhibitors, Wee1 Inhibitors, AML
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZN-d5 ZN-c3Drug
Also called Study Drug
Oral agent
ZN-c3Drug
Also called Study Drug
Oral agent
| Study group | Role | What they receive |
|---|---|---|
| Acute Myeloid Leukemia | Experimental | Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination
Phase 2: Dose Expansion Receives: Drug: ZN-d5 ZN-c3; Drug: ZN-c3 |
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: At the end of Cycle 1 (each cycle is 28 days)
Incidence, severity, and relatedness of adverse events( AEs)
Measured: Through study completion, typically < 12 months
Secondary outcomes (5)
1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration
The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined
Measured: Through study completion, typically <12 months
2. To investigate the plasma PK of ZN-c3 when given as monotherapy - Area under the plasma concentration-time curve from 0 to 24h
Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) will be determined
Measured: Through study completion, typically < 12 months
5. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Maximum Plasma Concentration
The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) and ZN-d5 (and its potential metabolites, as applicable) will be determined
Measured: Through study completion, typically < 12 months
6. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Area under the plasma concentration-time curve from 0 to 24h
Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) and ZN-d5 (and its potential metabolites, as applicable) will be determined
Measured: Through study completion, typically < 12 months
Rate and duration or 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 posted12 Jan 2023
- Study start1 Dec 2022
- Primary completion2 Jul 2024
- Study completion26 Jul 2024
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia (AML)Studies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 40 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 wholly owned subsidiary of Zentalis Pharmaceuticals, Inc., Study director, K-Group Alpha
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05682170
- Sponsor's protocol ID
- ZN-d5-004C
- Status last verified
- Sep 2024
- First submitted
- 19 Dec 2022
- 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
- A Phase 1/2 Dose Escalation Study of the BCL-2 Inhibitor ZN-d5 and the WEE1 Inhibitor ZN-c3 in Subjects With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT05682170
- Acronym / sponsor ID
- ZN-d5-004C
- Conditions
- Acute Myeloid Leukemia (AML)
- Keywords
- BCL-2 Inhibitors, Wee1 Inhibitors, AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 40 participants (actual)
- Lead sponsor
- K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 2 Jul 2024 (actual)
- Study completion
- 26 Jul 2024 (actual)
- First posted
- 12 Jan 2023 (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.
A Phase 1/2 dose escalation study of BCL-2 Inhibitor ZN-d5 and the Wee1 Inhibitor ZN-c3 in Subjects with Acute Myeloid Leukemia (AML).
Detailed description
This is an open-label multicenter Phase 1/2 dose escalation study, evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2 inhibitor ZN-d5 and Wee1 inhibitor ZN-c3 in subjects with AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute Myeloid Leukemia | Experimental | Drug: ZN-d5 ZN-c3, Drug: ZN-c3Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination Phase 2: Dose Expansion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adults with AML (including secondary or therapy-related), relapsed from or refractory to one or more prior lines of therapy, which may include venetoclax except in Expansion Cohort A
- ECOG performance status score ≤2.
- Projected life expectancy of at least 12 weeks.
- Estimated glomerular filtration rate ≥60 mL/min
- Women of childbearing potential must not be pregnant and must use effective birth control during the study and for 6 months after the last dose of study drugs.
Key exclusion criteria (8 listed)
- Known active CNS involvement
- Diagnosis of acute promyelocytic leukemia.
- Peripheral blast count of >25 × 109/L (cytoreduction permitted).
- Adequate washout from prior therapy including hematopoietic stem cell transplant and recovery from prior treatment-related toxicities to Grade 2 or lower
- Significant cardiovascular disease
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-d5 ZN-c3Also: Study DrugOral agent | Drug | Acute Myeloid Leukemia |
| ZN-c3Also: Study DrugOral agent | Drug | Acute Myeloid Leukemia |
Primary outcome
Observed dose limiting toxicities
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Observed Dose Limiting Toxicities (DLTs) in DLT evaluable subjects.
Incidence, severity, and relatedness of adverse events( AEs)
Time frame: Through study completion, typically < 12 months
5 secondary outcomes
1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration
Time frame: Through study completion, typically <12 months
2. To investigate the plasma PK of ZN-c3 when given as monotherapy - Area under the plasma concentration-time curve from 0 to 24h
Time frame: Through study completion, typically < 12 months
5. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Maximum Plasma Concentration
Time frame: Through study completion, typically < 12 months
6. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Area under the plasma concentration-time curve from 0 to 24h
Time frame: Through study completion, typically < 12 months
Rate and duration or remission according to the European LeukemiaNet 2017 criteria
Time frame: Through study completion, typically < 12 months
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
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 wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. study director
K-Group Alpha
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZN-d5 ZN-c3 and ZN-c3 in people with Acute Myeloid Leukemia (AML), run by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. at 13 sites in United States.
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 6 inclusion and 8 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: stopped early, 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 13 sites in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: Sponsor decision). Results are not available in the source record.
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: At the end of Cycle 1 (each cycle is 28 days)). 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.