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A Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With 7+3 Induction Chemotherapy in Patients With Acute Myeloid Leukemia

Phase 1
18 Years
Open (Enrolling)
Acute Myelogenous Leukemia

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Trial Information

A Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With 7+3 Induction Chemotherapy in Patients With Acute Myeloid Leukemia

If you agree to take part in this study you will be asked to undergo some screening tests or
procedures to find out if you can be in the research study. Many of these tests and
procedures are likely to be part of regular cancer care and may be done even if it turns out
that you do not take part in the research study. If you have had some of these tests or
procedures recently, they may or may not need to be repeated. These tests and procedures
include: a medical history, physical exam, performance status, urine test,
Electrocardiogram, Echocardiogram, blood tests and a bone marrow aspirate/biopsy. If these
tests show that you are eligible to participate in the research study, you will begin the
study treatment. If you do not meet the eligibility criteria, you will not be able to
participate in this research study.

You will begin treatment with idarubicin, and cytarabine followed by alisertib several days
later (on day 8). Not everyone who participates in this research study will receive the same
dose of the study drug. The dose you get will depend on the number of participants who have
been enrolled in the study before you and how well they have tolerated their doses. The
following assessments will be completed while on trial: physical exam, performance status,
urine test, blood tests, bone marrow aspirate/biopsy.

The first part of the study procedure is called "induction". During induction you will be
admitted to the hospital on an in-patient basis. You will receive cytarabine and idarubicin
by IV (intravenously or through a vein). Cytarabine will be given by continuous IV infusion
for seven days, beginning on Day 1. Idarubicin will be given once each day as an IV
injection for a total of three days, beginning on the same day as cytarabine. If idarubicin
is not available, you may receive a very similar chemotherapy in its place called
daunorubicin. Alisertib will be given orally (by mouth) twice a day for one week. It will
start on the second week of treatment.

A bone marrow biopsy will be performed at approximately 14 days after the start of
chemotherapy. If the results of this biopsy detect residual leukemia in the bone marrow,
your physicians may give you another round of induction therapy. However, this time,
cytarabine will be given by continuous IV infusion for only five days, and idarubicin will
be given once each day as an IV injection for a total of 2 days, again beginning on the same
day as cytarabine.

If at the end of the first cycle of induction (whether you've received one round or two
rounds of induction) the number of leukemia cells have not decreased as much as expected or
desired, you will be removed from the study and given alternative options.

The second part of study procedure is called "consolidation". If you have achieved a
remission after your induction phase, you are not a candidate for a bone marrow transplant,
and you tolerated study drug well during induction, you may receive consolidation treatment.
Soem participants may not receive consolidation therapy on this trial, based on the advice
of their treating physician.

For consolidation, you will receive a higher dose of cytarabine than you did during
induction. You will be hospitalized and cytarabine will be given daily as an IV infusion for
five days. Alisertib will also be given during the consolidation phase of therapy. It will
start at the end of the cytarabine administration and be given for a total of seven days.
You may receive up to four cycles of consolidation treatment, depending on your disease and
the discretion of your treating physician.

The third part of study procedures is called "maintenance". After the induction course of
therapy, your physician may begin consolidation therapy. If this is the case, you will start
maintenance therapy after finishing consolidation therapy. If consolidation is not done, the
maintenance phase will start after induction.

During maintenance, you will take alisertib twice daily for a period of seven days, followed
by a two week break without treatment. This one week of therapy, followed by two weeks off
therapy, will be a 21-day cycle. It will be repeated until 12 months have passed from the
start of the maintenance therapy phase. During this phase, participants will not receive
other chemotherapies and will not be hospitalized for treatment. They will take alisertib at
home and will be followed in clinic for monitoring. During the maintenance phase, we will
continue to collect approximately 2 to 3 teaspoons of blood for research purposes
intermittently on your visits to clinic.

After the final dose of the study drug we would like to keep track of your medical condition
and overall health following the 12 months of alisertib. We may ask you questions about your
general health, current medications, and disease status. We will also check on any new
anticancer therapy you may have started.

Inclusion Criteria:

- Pathologically confirmed, newly diagnosed acute myelogenous leukemia

- Agree to use an acceptable method for contraception during the entire study treatment
period through 4 months after the last dose of MLN8237

- Able to take oral medication and to maintain a fast as required for 2 hours before
and 1 hour after MLN8237 administration

Exclusion Criteria:

- Have received systemic antineoplastic therapy, including radiotherapy within 14 days
of study treatment, with the exception of hydroxyurea or 6-mercaptopurine for the
purposes of cytoreduction

- Pregnant or breastfeeding

- Presence of "favorable" or "better risk" cytogenic prognosis

- Prior allogeneic bone marrow or organ transplantation

- Diagnosis of acute bilineal/biphenotypic leukemia

- History of a different malignancy except if disease-free for at least 5 years and at
low risk or recurrence; or cervical cancer in situ, basal cell or squamous cell
carcinoma of the skin within the past 5 years

- Uncontrolled intercurrent illness

- HIV positive on combination antiretroviral therapy

- Diagnosis of active hepatitis B or C

- Current or history of congestive heart failure NYHA class 3 or 4, or documented
diastolic or systolic dysfunction

- Current or history of ventricular or life threatening arrhythmias or diagnosis of
long QT syndrome

- Known history of uncontrolled sleep apnea syndrome or other condition that could
result in excessive daytime sleepiness

- Requirement for constant administration of proton pump inhibitor, H2 antagonist or
pancreatic enzymes

- Systemic infection requiring IV antibiotic therapy within 14 days of first dose of
study drug

- Treatment with clinically significant enzyme inducers

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose of Alisertib in combination with 7+3 induction chemotherapy

Outcome Description:

The maximum tolerated dose (MTD) of the aurora kinase A inhibitor alisertib (MLN8237) in combination with 7+3 induction chemotherapy in patients with acute myeloid leukemia

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Amir Fathi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

April 2013

Completion Date:

Related Keywords:

  • Acute Myelogenous Leukemia
  • Newly diagnosed
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Dana-Farber Cancer Institute Boston, Massachusetts  02115
Brigham and Women's Hospital Boston, Massachusetts  02115
Massachusetts General Hospital Boston, Massachusetts  02114-2617