Acute Myeloid LeukemiaPhase 1NCT04081259
LY3214996 in Patients With AML Who Are Not Candidates for Standard Therapy
A Phase 1 study testing LY3214996 in people with Acute Myeloid Leukemia, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study is evaluating a targeted therapy as a possible treatment for acute myeloid leukemia (AML) that has returned or not responded to standard treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- LY3214996
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2020to 26 Aug 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
- Participants must have histologically confirmed acute myeloid leukemia (AML) diagnosed per WHO criteria.
- Participants must have relapsed or refractory AML.
- Age ≥ 18 years.
- ECOG performance status ≤ 2
- Participants must have adequate organ function as defined below:
- Direct Bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
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- AST (SGOT) and ALT(SGPT) ≤ 2.5 × institutional ULN, OR
- AST (SGOT) and ALT (SGPT) ≤ 5 × institutional ULN if elevation is a result of leukemia
- Creatinine Clearance ≥ 60 mL/min/1.73 m2 (calculated via the Cockcroft-Gault equation)
- The effects of LY3214996 on the developing human fetus are unknown. For this reason and because anti-cancer agents are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of LY3214996 administration.
- Ability to understand and the willingness to sign a written informed consent document.
- Ability to swallow and retain oral medication.
- Participants must have resolution of adverse events related to prior anti-cancer therapies to ≤ CTCAE Grade 2 or baseline
- Considerations of concurrent use of CYP3A4 inhibitors
- Dose escalation phase:
- ARM A: Participants must not be receiving any concurrent antifungal agents that are moderate/strong CYP3A4 inhibitors. These include but are not limited to: isavuconazole, itraconazole, fluconazole, ketoconazole, posaconazole, and voriconazole.
- ARM B: Participants must be receiving concurrent antifungal agents that are moderate/strong CYP3A4 inhibitors. These include but are not limited to: isavuconazole, itraconazole, fluconazole, ketoconazole, posaconazole, and voriconazole.
- Expansion Phase:
- Participants not receiving concurrent antifungal agents that are moderate/strong CYP3A4 inhibitors are eligible to enroll at MTD determined upon completion of dose-escalation cohort Arm A. Participants receiving concurrent antifungal agents that are moderate/strong CYP3A4 inhibitors are eligible to enroll at MTD determined upon completion of dose-escalation cohort Arm B.
Who cannot join
- Participants who have had chemotherapy, other investigational therapy, immunotherapy, or radiotherapy within 2 weeks prior to the first dose of study medication. ATRA treatment is permitted with no required washout if treatment duration was for less than 1 week. Hydroxyurea is allowed with no required washout. For participants with an absolute peripheral blast count > 20 K/µL, hydroxyurea may be administered up to day 14 of protocol therapy with a maximum allowed dose of 6 g per day.
- Participants who have received oral tyrosine kinase inhibitors (TKIs) within 5 half-lives of the first dose of study medication.
- Participants who have had major surgery within 4 weeks prior to the first dose of study medication.
- Participants who have had a prior stem cell transplant (SCT) within 90 days prior to the first dose of study medication. Additionally, participants having undergone prior SCT must be off calcineurin inhibitor therapy for at least 28 days prior to the first dose of study medication.
- Participants with active > Grade 1 acute or chronic Graft v. Host Disease (GvHD) who are receiving immunosuppressive therapy other than prednisone. Use of prednisone is permitted only if participants have been maintained at a steady dose of < 20 mg/day for at least 5 days prior to the first dose of study medication.
- Participants with known active CNS leukemia involvement. Participants with no known history of CNS leukemia are not required to undergo lumbar puncture (LP) for trial eligibility unless the participant is symptomatic as judged by the treating investigator. Participants with a history of CNS leukemia involvement are eligible provided that the CNS disease has been adequately treated and cleared prior to study enrollment as judged by the treating investigator.
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- History of allergic reactions attributed to compounds of similar chemical or biologic composition to LY3214996.
- Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because LY3214996 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with LY3214996, breastfeeding should be discontinued if the mother is treated with LY3214996. A negative serum pregnancy test is required for women of childbearing potential prior to study entry.
- Participants who are known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B or C. Testing is not required for eligibility.
- Participants with a history or findings of central or branch retinal artery or venous occlusion with significant vision less, or other retinal diseases causing visual impairment as determined by an ophthalmologist.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: A Phase 1 Study of LY3214996, an ERK1/2 Inhibitor, in Patients With AML Who Are Not Candidates for Standard Therapy
This research study is evaluating a targeted therapy as a possible treatment for acute myeloid leukemia (AML) that has returned or not responded to standard treatment.
Read the detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved LY3214996 as a treatment for any disease.
LY3214996 is an extracellular signal-regulated kinase (ERK) inhibitor that is being developed as a treatment for patients with advanced cancer. ERK inhibitors stop the signal that a cancer cell receives telling it to grow. In this research study, the investigators are testing to see if LY3214996 is a safe treatment for AML that has returned or not responded to standard treatment. Several doses of the study drug will be explored in this study.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- LY3214996
- Keywords
- Acute Myeloid Leukemia, AML, ERK, Relapsed, Refractory, LY3214996
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3214996Drug
LY3214996 is an extracellular signal-regulated kinase (ERK) inhibitor that is being developed as a treatment for patients with advanced cancer. ERK inhibitors stop the signal that a cancer cell receives telling it to grow.
| Study group | Role | What they receive |
|---|---|---|
| Arm B: Dose Escalation LY3214996 | Experimental | -LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle for patients with inhibitors for fungal prophylaxis/treatment Receives: Drug: LY3214996 |
| Arm A: Dose Expansion LY3214996 | Experimental | -LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle for patients without inhibitors for fungal prophylaxis/treatment Receives: Drug: LY3214996 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity
Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.
Measured: 21 days
Secondary outcomes (1)
Overall Response Rate
Rate of complete remission (CR), CR with incomplete count recovery (CRi), and partial remission (PR) using IWG and ELN criteria.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2019
- Study start15 Jul 2020
- Primary completion3 Aug 2023
- Study completion26 Aug 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.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- 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
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Rahul Vedula, MD, Dana-Farber Cancer Institute
- Investigators
- Rahul Vedula, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04081259
- Sponsor's protocol ID
- 19-263
- Status last verified
- May 2025
- First submitted
- 5 Sep 2019
- Last updated
- 8 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to the sponsor. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of LY3214996, an ERK1/2 Inhibitor, in Patients With AML Who Are Not Candidates for Standard Therapy
- ClinicalTrials.gov ID
- NCT04081259
- Acronym / sponsor ID
- 19-263
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Acute Myeloid Leukemia, AML, ERK, Relapsed, Refractory, LY3214996
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 15 Jul 2020 (actual)
- Primary completion
- 3 Aug 2023 (actual)
- Study completion
- 26 Aug 2023 (actual)
- First posted
- 9 Sep 2019 (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.
This research study is evaluating a targeted therapy as a possible treatment for acute myeloid leukemia (AML) that has returned or not responded to standard treatment.
Detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has not approved LY3214996 as a treatment for any disease.
LY3214996 is an extracellular signal-regulated kinase (ERK) inhibitor that is being developed as a treatment for patients with advanced cancer. ERK inhibitors stop the signal that a cancer cell receives telling it to grow. In this research study, the investigators are testing to see if LY3214996 is a safe treatment for AML that has returned or not responded to standard treatment. Several doses of the study drug will be explored in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm B: Dose Escalation LY3214996 | Experimental | Drug: LY3214996-LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle for patients with inhibitors for fungal prophylaxis/treatment |
| Arm A: Dose Expansion LY3214996 | Experimental | Drug: LY3214996-LY3214996 will be administered by mouth once daily continuously throughout each treatment cycle for patients without inhibitors for fungal prophylaxis/treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Participants must have histologically confirmed acute myeloid leukemia (AML) diagnosed per WHO criteria.
- Participants must have relapsed or refractory AML.
- Age ≥ 18 years.
- ECOG performance status ≤ 2
- Participants must have adequate organ function as defined below:
Key exclusion criteria (11 listed)
- Participants who have had chemotherapy, other investigational therapy, immunotherapy, or radiotherapy within 2 weeks prior to the first dose of study medication. ATRA treatment is permitted with no required washout if treatment duration was for less than 1 week. Hydroxyurea is allowed with no required washout. For participants with an absolute peripheral blast count > 20 K/µL, hydroxyurea may be administered up to day 14 of protocol therapy with a maximum allowed dose of 6 g per day.
- Participants who have received oral tyrosine kinase inhibitors (TKIs) within 5 half-lives of the first dose of study medication.
- Participants who have had major surgery within 4 weeks prior to the first dose of study medication.
- Participants who have had a prior stem cell transplant (SCT) within 90 days prior to the first dose of study medication. Additionally, participants having undergone prior SCT must be off calcineurin inhibitor therapy for at least 28 days prior to the first dose of study medication.
- Participants with active > Grade 1 acute or chronic Graft v. Host Disease (GvHD) who are receiving immunosuppressive therapy other than prednisone. Use of prednisone is permitted only if participants have been maintained at a steady dose of < 20 mg/day for at least 5 days prior to the first dose of study medication.
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 |
|---|---|---|
| LY3214996LY3214996 is an extracellular signal-regulated kinase (ERK) inhibitor that is being developed as a treatment for patients with advanced cancer. ERK inhibitors stop the signal that a cancer cell receives telling it to grow. | Drug | Arm A: Dose Expansion LY3214996, Arm B: Dose Escalation LY3214996 |
Primary outcome
Dose Limiting Toxicity
Time frame: 21 days
Toxicities occurring following administration of protocol therapy, measured using CTCAE 5.0 criteria.
1 secondary outcome
Overall Response Rate
Time frame: 6 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 8 May 2025.
- Individual participant dataSharing planned: Yes. The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to the sponsor. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
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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.
Rahul Vedula, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY3214996 in people with Acute Myeloid Leukemia, run by Dana-Farber Cancer Institute at 1 site 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 19 inclusion and 11 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 8 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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?
Dose Limiting Toxicity (time frame: 21 days). 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 8 May 2025.