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Alisertib for Acute Myeloid Leukemia

This study has been completed.
Information provided by (Responsible Party):
Amir Fathi, Massachusetts General Hospital Identifier:
First received: January 25, 2013
Last updated: February 15, 2017
Last verified: February 2017

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.

Condition Intervention Phase
Acute Myelogenous Leukemia
Drug: Cytarabine
Drug: Idarubicin
Drug: Alisertib
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With 7+3 Induction Chemotherapy in Patients With Acute Myeloid Leukemia

Resource links provided by NLM:

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Maximum Tolerated Dose of Alisertib in combination with 7+3 induction chemotherapy [ Time Frame: 2 years ]
    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

  • Evaluate safety and tolerability of alisertib, including number of adverse events and severity. [ Time Frame: 2 years ]
    The number and severity of adverse events associated with this treatment.

Secondary Outcome Measures:
  • Severity and number of all trial-related toxicities [ Time Frame: 2 years ]
    To detect and categorize, according to severity, the cumulative incidences of drug related toxicities

  • Rates of response [ Time Frame: 2 years ]
    To determine the response rate, including rates of complete and partial remission

  • One-year relapse-free and overall survival [ Time Frame: 2 years ]
    To measure the one-year relapse-free and overall survival after treatment

  • Measurement of tumor mitotic index, Ki67 and cPARP statining, Pharmacodynamic parameters for aurora kinase A inhibition, during treatment [ Time Frame: 2 years ]
    To assess pharmacodynamic effects of aurora kinase A inhibition, including tumor mitotic index, Ki67 and cPARP staining

Enrollment: 22
Study Start Date: April 2013
Study Completion Date: November 2016
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

Induction: 100 mg/m2/day Cytarabine intravenous, days 1-7 of induction cycle. 12 mg/m2/day Idarubicin intravenous, days 1-3. Alisertib orally, twice a day for one week starting on day 8, dose escalation-starting dose 10 mg PO BID.

Consolidation: Cytarabine 3 g/m2 by IV infusion over 3 hours given every 12 hours on Days 1, 3 and 5 (subjects younger than age 60) or Cytarabine 2 g/m2 per day by IV infusion over 3 hours on days 1-5 (subjects at or older than age 60)

Drug: Cytarabine Drug: Idarubicin Drug: Alisertib
Other Name: MLN8237

  Show Detailed Description


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01779843

United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
Principal Investigator: Amir Fathi, MD Massachusetts General Hospital
  More Information

Responsible Party: Amir Fathi, Principal Investigator, Massachusetts General Hospital Identifier: NCT01779843     History of Changes
Other Study ID Numbers: 12-531
Study First Received: January 25, 2013
Last Updated: February 15, 2017

Keywords provided by Massachusetts General Hospital:
Newly diagnosed

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors processed this record on April 28, 2017