Neoplasms

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Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

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

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)

Merestinib

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.

LY2874455

Jacqueline S. Garcia, MD

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

* 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.

open-label phase 1 study using a 3+3 design with planned dose escalation

Combination Merestinib and LY2874455 for Patients With Relapsed or Refractory Acute Myeloid Leukemia

A Phase 1 Study of Merestinib in Combination With LY2874455 in Relapsed or Refractory Acute Myeloid Leukemia

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.

Time to event summaries will use the Kaplan-Meier method.

Standard noncompartmental pharmacokinetic analysis will be employed including AUC 0-24 after initial and repeat administration.

Standard noncompartmental pharmacokinetic analysis will be employed including peak drug plasma concentration (Cmax) after initial and repeat administration.

Spots Global Cancer Trial Database for relapsed adult acute myeloid leukemia