Alisertib for Acute Myeloid Leukemia

STATUS: Recruiting

Phase: 1

Diagnosis: Leukemia/MDS

NCT ID: NCT01779843 (View complete trial on ClinicalTrials.gov)

DFCI Protocol ID: 12-531

This research study is a Phase I clinical trial. Phase I trials test the safety of an investigational drug or combination of drugs. Phase I studies also try to define the appropriate dose of the investigational drug to use for further studies. "Investigational" means that the combination of drugs is still being studied and that research doctors are trying to find out more about it. As part of this research study, you will take alisertib in combination with idarubicin and cytarabine. Alisertib has not been approved by the FDA for your cancer. However, cytarabine and idarubicin have both been approved by the FDA for treatment of AML. It also means that the FDA has not approved giving alisertib with idarubicin and cytarabine for use in patients, including patients with your type of cancer. Idarubicin and cytarabine are chemotherapy agents that are commonly used to treat individuals diagnosed with AML. Alisertib has been used in laboratory studies and those studies suggest that alisertib may slow down the spread of your cancer. It does this by blocking certain substances needed by the cancer cells to spread. In this study, researchers would like to combine alisertib with standard chemotherapy (cytarabine and idarubicin) in order to see if it can be given safely with chemotherapy in individuals with AML. The primary purpose of this research study is to determine the highest dose that alisertib can be given with idarubicin and cytarabine without severe or unmanageable side effects. The dose identified in this study will be used in future research studies.

Conducting Institutions:

Massachusetts General Hospital, Dana-Farber Cancer Institute, Brigham and Women's Hospital

Overall PI:

Amir Fathi, M.D., Massachusetts General Hospital

Site-responsible Investigators:

Daniel DeAngelo, MD, Dana-Farber Cancer Institute


Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100,

Dana-Farber Cancer Institute: Ilene Galinsky, 617-632-3902, igalinsky@partners.org

Eligibility Criteria

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