Relapsed Adult Acute Myeloid LeukemiaPhase 1NCT03125239
Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1 study testing Merestinib and LY2874455 in people with Relapsed Adult Acute Myeloid Leukemia and Refractory Adult Acute Myeloid Leukemia, run by Jacqueline Garcia, MD at 2 sites in United States.
Trial summary
This research study is studying a combination of two targeted therapies as a possible treatment for acute myeloid leukemia (AML) that has relapsed after initial treatment or did not fully respond. The name of the study interventions involved in this study are: Merestinib LY2874455 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Adult Acute Myeloid Leukemia, Refractory Adult Acute Myeloid Leukemia
- What is being tested?
- Merestinib and LY2874455
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesUnited States
- Study dates
- 10 Aug 2017to 1 Jun 2020
- 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 pathologically confirmed relapsed or refractory acute myeloid leukemia (AML) or secondary AML following IWG criteria [40].
- For subjects with relapsed AML: evidence of ≥ 5% blasts in the bone marrow or development of extramedullary disease who relapse after:
- Allogeneic hematopoietic stem cell transplant, or
- A minimum of one cycle of standard cytotoxic chemotherapy or two cycles of any hypomethylating agent-based therapy
- For subjects with refractory AML: a minimum of 2 prior induction regimens (example: patients who receive 7+3 followed by 5+2 would count as one induction regimen) or a minimum of two cycles of any hypomethylating agent-based therapy.
- For subjects with secondary AML: untreated secondary AML, must have been previously treated for myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) or MDS/MPN (MDS/MPN) overlap syndrome.
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- No limit to number of prior therapies.
- Patients are considered to have failed available therapies or to be ineligible for or to not be interested in intensive chemotherapies, including allogeneic hematopoietic stem cell transplantation.
- Patients with a history of allogeneic stem cell transplantation are eligible for study participation provided the transplant was > 100 days prior to study enrollment. Patients must not have active graft versus host disease other than grade 1 skin involvement.
- Age 18 and older.
- ECOG performance status ≤2 (see Appendix A).
- Participants must have normal organ and marrow function as defined below:
- Direct bilirubin within ≤ 1.5 times the institutional upper limit of normal (ULN). For patients with known Gilbert Syndrome, or if the elevation is believed to be leukemia related, the cut-off of ≤ 3.0 times the institutional ULN is allowable.
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN, unless believed to be leukemia related then ≤ 5 x ULN is allowed.
- Serum creatinine ≤ 2.0 x ULN
- Females of child bearing potential and males must agree to use barrier method/hormonal methods from start of study until four months after last dose of study drug. Females of child bearing potential must have a negative serum pregnancy test at screening. Females are not considered to be of child bearing potential if they are status post successful surgical sterilization including hysterectomy, bilateral tubal ligation or bilateral oophorectomy, or if they are postmenopausal (absence of menses for 12 consecutive months that is not secondary to prior chemotherapy, anti-estrogens, ovarian suppression or other reversible cause).
- The effects of Merestinib and LY2874455 on the developing human fetus are unknown. Small molecular inhibitors of tyrosine kinase receptors are known to be teratogenic. 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.
- Ability to understand and the willingness to sign a written informed consent document.
- Able and willing to undergo the required bone marrow biopsies. Correlative studies are strongly encouraged.
Who cannot join
- Participants who have had radiotherapy within 2 weeks, with the exception of localized radiotherapy to palliate extramedullary leukemia where no washout is required.
- Participants who have had chemotherapy within 2 weeks or 5 half-lives (whichever is longer) from the last dose of chemotherapy prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Hydroxyurea is allowed per treating investigator. IT chemotherapy prophylaxis is permitted.
- Participants who are receiving any other investigational agents, with the exception of topical or ophthalmologic therapies for mild graft versus host disease which are permitted.
- Participants with known CNS leukemia involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Individuals with other active malignancies that require concurrent chemotherapy are ineligible. Hormone therapy is allowed.
- Subject has a known gastrointestinal disorder that in the opinion of the treating investigator is concerning for malabsorption of oral medications.
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- Subject is unable to swallow pills.
- 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. Patients with current or history of NYHA class III or IV cardiac disease, myocardial infarction with past 6 months, or unstable arrhythmia will be ineligible for study.
- Pregnant women are excluded from this study because Merestinib and LY2874455 have 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 Merestinib and LY2874455, breastfeeding should be discontinued if the mother is treated with Merestinib and LY2874455.
- HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Merestinib and LY2874455. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
- Subjects with QTcF interval of ≥ 450 msec if male and ≥ 470 msec if female following or with other factors increase the risk of QT prolongation or arrhythmic events (e.g. heart failure, hypokalemia, family history of long QT interval syndrome) at screening. Subjects with bundle branch block should be reviewed by the Medical Monitor for potential inclusion.
- Subjects with known active HBV or HCV (cannot have an elevated viral load of HBV or HCV if known history) are ineligible
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Phase 1 Study of Merestinib in Combination With LY2874455 in Relapsed or Refractory Acute Myeloid Leukemia
This research study is studying a combination of two targeted therapies as a possible treatment for acute myeloid leukemia (AML) that has relapsed after initial treatment or did not fully respond.
The name of the study interventions involved in this study are:
- Merestinib
- LY2874455
Read the detailed description
- This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
- The FDA (the U.S. Food and Drug Administration) has not approved Merestinib or LY2874455 as a treatment for any disease.
- Merestinib is an oral drug known as a MET kinase inhibitor that is being developed as a treatment for patients with advanced cancer. MET inhibitors work by stopping a signal that a cell receives instructing it to grow.
- LY2874455 is an oral drug known as an FGFR inhibitor that is also being developed as a treatment for patients with advanced cancer. FGFR inhibitors work by stopping a signal that a cell receives instructing it to grow.
- In this research study, the investigators are investigating whether Merestinib and LY2874455 is safe to give in combination in patients with AML. In previous laboratory studies, it was found that leukemia cells responded to treatment with a MET inhibitor and an FGFR inhibitor. However, it is not yet known whether this will also be the case with LY2874455 and merestinib when given to participants.
- Being tested
- Merestinib, LY2874455
- Keywords
- Refractory Adult Acute Myeloid Leukemia, Relapsed Adult Acute Myeloid Leukemia
- 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.
MerestinibDrug
Also called LY2801653
Oral, once a day, Merestinib Only- Lead in period on week. The followed by cycles on combination therapy with Merestinib and LY2874455 (28 days long)
LY2874455Drug
This will be followed by cycles of combination therapy with merestinib and LY2874455. Each of these cycles are 28 days long. • LY2874455 will be taken by mouth twice a day. You may take LY2874455 twice daily for 14 days, 21 days, or 28 days each cycle depending on the dose level you are assigned.
| Study group | Role | What they receive |
|---|---|---|
| Merestinib and LY2874455 | Experimental | Patients who fulfill eligibility criteria will be entered into the trial to receive Merestinib and LY2874455.
After the screening procedures confirm participation in the research study:
* The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have AML, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.
* Merestinib
* LY2874455 Receives: Drug: Merestinib; Drug: LY2874455 |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD of LY2874455 and Merestinib
Dose-escalation will follow a standard 3+3 design exploring 3 dose levels of LY2874455 with a steady dose of Merestinib. We will escalate to next dose cohort if 0/3 or 1/6 participants have a DLT during the first cycle of therapy. If the rate of dose limiting toxicity (DLT) exceeds 30%, it is less likely that the dose of LY2874455 will be escalated.
Measured: 35 Days
Secondary outcomes (6)
Best Overall response
Time to event summaries will use the Kaplan-Meier method.
Measured: Up to 1 year
Duration of Remission
Time to event summaries will use the Kaplan-Meier method.
Measured: Up to 1 year
Progression Free Survival
Time to event summaries will use the Kaplan-Meier method.
Measured: Up to 1 year
Overall Survival
Time to event summaries will use the Kaplan-Meier method.
Measured: Up to 1 year
PK of Merestinib and LY2874455 in AML during the dose escalation part of the study: AUC
Standard noncompartmental pharmacokinetic analysis will be employed including AUC 0-24 after initial and repeat administration.
Measured: 35 days
PK of Merestinib and LY2874455 in AML during the dose escalation part of the study: Cmax
Standard noncompartmental pharmacokinetic analysis will be employed including peak drug plasma concentration (Cmax) after initial and repeat administration.
Measured: 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2017
- Study start10 Aug 2017
- Primary completion1 Jun 2020
- Study completion1 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Adult 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
- Not applicable
- Intervention model
- Single group
- Model description
- open-label phase 1 study using a 3+3 design with planned dose escalation
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jacqueline Garcia, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor-investigator, Jacqueline Garcia, MD, Dana-Farber Cancer Institute
- Investigators
- Jacqueline S. Garcia, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03125239
- Sponsor's protocol ID
- 17-099
- Status last verified
- Jun 2020
- First submitted
- 17 Apr 2017
- Last updated
- 30 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of Merestinib in Combination With LY2874455 in Relapsed or Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03125239
- Acronym / sponsor ID
- 17-099
- Keywords
- Refractory Adult Acute Myeloid Leukemia, Relapsed Adult Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Jacqueline Garcia, MDUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 10 Aug 2017 (actual)
- Primary completion
- 1 Jun 2020 (actual)
- Study completion
- 1 Jun 2020 (actual)
- First posted
- 24 Apr 2017 (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 studying a combination of two targeted therapies as a possible treatment for acute myeloid leukemia (AML) that has relapsed after initial treatment or did not fully respond.
The name of the study interventions involved in this study are:
- Merestinib
- LY2874455
Detailed description
- This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied.
- The FDA (the U.S. Food and Drug Administration) has not approved Merestinib or LY2874455 as a treatment for any disease.
- Merestinib is an oral drug known as a MET kinase inhibitor that is being developed as a treatment for patients with advanced cancer. MET inhibitors work by stopping a signal that a cell receives instructing it to grow.
- LY2874455 is an oral drug known as an FGFR inhibitor that is also being developed as a treatment for patients with advanced cancer. FGFR inhibitors work by stopping a signal that a cell receives instructing it to grow.
- In this research study, the investigators are investigating whether Merestinib and LY2874455 is safe to give in combination in patients with AML. In previous laboratory studies, it was found that leukemia cells responded to treatment with a MET inhibitor and an FGFR inhibitor. However, it is not yet known whether this will also be the case with LY2874455 and merestinib when given to participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open-label phase 1 study using a 3+3 design with planned dose escalation
| Arm | Type | Receives |
|---|---|---|
| Merestinib and LY2874455 | Experimental | Drug: Merestinib, Drug: LY2874455Patients who fulfill eligibility criteria will be entered into the trial to receive Merestinib and LY2874455. After the screening procedures confirm participation in the research study: * The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have AML, not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated. * Merestinib * LY2874455 |
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 pathologically confirmed relapsed or refractory acute myeloid leukemia (AML) or secondary AML following IWG criteria [40].
- No limit to number of prior therapies.
- Patients are considered to have failed available therapies or to be ineligible for or to not be interested in intensive chemotherapies, including allogeneic hematopoietic stem cell transplantation.
- Patients with a history of allogeneic stem cell transplantation are eligible for study participation provided the transplant was > 100 days prior to study enrollment. Patients must not have active graft versus host disease other than grade 1 skin involvement.
- Age 18 and older.
Key exclusion criteria (12 listed)
- Participants who have had radiotherapy within 2 weeks, with the exception of localized radiotherapy to palliate extramedullary leukemia where no washout is required.
- Participants who have had chemotherapy within 2 weeks or 5 half-lives (whichever is longer) from the last dose of chemotherapy prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. Hydroxyurea is allowed per treating investigator. IT chemotherapy prophylaxis is permitted.
- Participants who are receiving any other investigational agents, with the exception of topical or ophthalmologic therapies for mild graft versus host disease which are permitted.
- Participants with known CNS leukemia involvement should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- Individuals with other active malignancies that require concurrent chemotherapy are ineligible. Hormone therapy is allowed.
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 |
|---|---|---|
| MerestinibAlso: LY2801653Oral, once a day, Merestinib Only- Lead in period on week. The followed by cycles on combination therapy with Merestinib and LY2874455 (28 days long) | Drug | Merestinib and LY2874455 |
| LY2874455This will be followed by cycles of combination therapy with merestinib and LY2874455. Each of these cycles are 28 days long. • LY2874455 will be taken by mouth twice a day. You may take LY2874455 twice daily for 14 days, 21 days, or 28 days each cycle depending on the dose level you are assigned. | Drug | Merestinib and LY2874455 |
Primary outcome
MTD of LY2874455 and Merestinib
Time frame: 35 Days
Dose-escalation will follow a standard 3+3 design exploring 3 dose levels of LY2874455 with a steady dose of Merestinib. We will escalate to next dose cohort if 0/3 or 1/6 participants have a DLT during the first cycle of therapy. If the rate of dose limiting toxicity (DLT) exceeds 30%, it is less likely that the dose of LY2874455 will be escalated.
6 secondary outcomes
Best Overall response
Time frame: Up to 1 year
Duration of Remission
Time frame: Up to 1 year
Progression Free Survival
Time frame: Up to 1 year
Overall Survival
Time frame: Up to 1 year
PK of Merestinib and LY2874455 in AML during the dose escalation part of the study: AUC
Time frame: 35 days
PK of Merestinib and LY2874455 in AML during the dose escalation part of the study: Cmax
Time frame: 35 days
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 30 Jun 2020.
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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.
Jacqueline S. Garcia, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Merestinib and LY2874455 in people with Relapsed Adult Acute Myeloid Leukemia and Refractory Adult Acute Myeloid Leukemia, run by Jacqueline Garcia, MD at 2 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 19 inclusion and 12 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 30 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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?
MTD of LY2874455 and Merestinib (time frame: 35 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 30 Jun 2020.