Clinical Trial: MEK Inhibitor MEK162, Idarubicin, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase I Study of MEK Inhibitor MEK162 Combined With Idarubicin and Cytarabine Induction in Patients With Relapsed/Refractory RAS-Mutated Acute Myeloid Leukemia

Brief Summary: This phase I trial studies the MEK inhibitor MEK162 to see if it is safe in patients when combined with idarubicin and cytarabine. MEK inhibitor MEK162 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving MEK inhibitor MEK162, cytarabine, and idarubicin may be an effective treatment for acute myeloid leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine maximum tolerated dose (MTD) of MEK162 (MEK inhibitor MEK162) in patients with RAS-mutated acute myeloid leukemia (AML) when combined with sequential induction chemotherapy (3+4) as measured by development of grade 3-4 dose-limiting toxicities (DLT).

SECONDARY OBJECTIVES:

I. Analyze downstream inhibition of RAS signaling following therapy with single-agent MEK162 with exploratory pharmacodynamics (PD) studies.

II. Perform preliminary efficacy analysis of combination of MEK162 and induction chemotherapy (3+4) in patients with RAS-mutated AML by measuring complete remission rate, 2-year overall survival, and duration of response.

OUTLINE:

INDUCTION THERAPY: Patients receive MEK inhibitor MEK162 orally (PO) twice daily (BID) on days -4 to -1 and days 5-18, cytarabine intravenously (IV) continuously over 24 hours on days 1-4, and idarubicin IV over 1 hour on days 1-3. Patients may receive a second course of induction at the discretion of the principal investigator.

POST-REMISSION THERAPY: Patients receive cytarabine IV continuously over 24 hours on days 1-3, idarubicin IV over 1 hour on days 1 and 2, and MEK inhibitor MEK 162 PO BID on days 4-17. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.


Sponsor: Bruno C. Medeiros

Current Primary Outcome: MTD of MEK inhibitor MEK162 in combination with chemotherapy, defined as the dose associated with a dose-limiting toxicity rate of 35% assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: 28 days ]

Dose limiting toxicities will be tabulated by dose, severity and major organ system.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Pharmacodynamic analysis of downstream inhibition of RAS signaling following therapy with single-agent MEK inhibitor MEK162 [ Time Frame: Day -4, -1, and 18 ]
    Pharmacodynamic correlative data will be summarized with medians and ranges for each dose group. If there are a sufficient number of patients assigned to both doses, the medians will be compared with a Wilcoxon Rank Sum test.
  • Complete remission rate, defined as bone marrow biopsy demonstrating < 5% blasts and recovery of peripheral blood counts after induction chemotherapy [ Time Frame: Up to day 19 ]
    The proportion of patients who achieve complete remission will be estimated overall with an exact 95% confidence interval; for descriptive purpose the same proportion at each dose will similarly described.
  • Overall survival [ Time Frame: Time of study entry to the time of death from any cause, assessed at 2 years ]
    The proportion of patients who achieve 2-year overall survival will be estimated overall with an exact 95% confidence interval; for descriptive purpose the same proportion at each dose will similarly described.
  • Duration of response [ Time Frame: Time of complete response to biopsy-documented recurrence of disease, assessed up to 4 years ]


Original Secondary Outcome: Same as current

Information By: Stanford University

Dates:
Date Received: January 28, 2014
Date Started: December 2014
Date Completion: October 2020
Last Updated: January 26, 2017
Last Verified: January 2017