Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03125239|
Recruitment Status : Recruiting
First Posted : April 24, 2017
Last Update Posted : August 14, 2018
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:
|Condition or disease||Intervention/treatment||Phase|
|Relapsed Adult Acute Myeloid Leukemia Refractory Adult Acute Myeloid Leukemia||Drug: Merestinib Drug: LY2874455||Phase 1|
- 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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||open-label phase 1 study using a 3+3 design with planned dose escalation|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of Merestinib in Combination With LY2874455 in Relapsed or Refractory Acute Myeloid Leukemia|
|Actual Study Start Date :||August 10, 2017|
|Estimated Primary Completion Date :||June 1, 2020|
|Estimated Study Completion Date :||June 1, 2020|
Experimental: Merestinib and LY2874455
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:
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)
Other Name: LY2801653
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.
- 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.
- Best Overall response [ Time Frame: Up to 1 year ]Time to event summaries will use the Kaplan-Meier method.
- Duration of Remission [ Time Frame: Up to 1 year ]Time to event summaries will use the Kaplan-Meier method.
- Progression Free Survival [ Time Frame: Up to 1 year ]Time to event summaries will use the Kaplan-Meier method.
- Overall Survival [ Time Frame: Up to 1 year ]Time to event summaries will use the Kaplan-Meier method.
- PK of Merestinib and LY2874455 in AML during the dose escalation part of the study: AUC [ Time Frame: 35 days ]Standard noncompartmental pharmacokinetic analysis will be employed including AUC 0-24 after initial and repeat administration.
- PK of Merestinib and LY2874455 in AML during the dose escalation part of the study: Cmax [ Time Frame: 35 days ]Standard noncompartmental pharmacokinetic analysis will be employed including peak drug plasma concentration (Cmax) after initial and repeat administration.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03125239
|Contact: Jacqueline S Garcia, MDfirstname.lastname@example.org|
|United States, Massachusetts|
|Brigham and Women's Hospital||Enrolling by invitation|
|Boston, Massachusetts, United States, 02115|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Jacqueline S Garcia, MD 617-632-6349 email@example.com|
|Principal Investigator: Jacqueline S Garcia, MD|
|Principal Investigator:||Jacqueline S. Garcia, MD||Dana-Farber Cancer Institute|