Alisertib for Acute Myeloid Leukemia

NCT01779843 | Completed Phase 1 DMC

• 1 other identifier: 12-531
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Acute Myelogenous Leukemia

Keywords

Newly diagnosed

Outcome Measures

Primary Outcomes (2)

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

  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

  2 years

• Evaluate safety and tolerability of alisertib, including number of adverse events and severity.

  The number and severity of adverse events associated with this treatment.

  2 years

Secondary Outcomes (4)

• Severity and number of all trial-related toxicities

  2 years

• Rates of response

  2 years

• One-year relapse-free and overall survival

  2 years

• Measurement of tumor mitotic index, Ki67 and cPARP statining, Pharmacodynamic parameters for aurora kinase A inhibition, during treatment

  2 years

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

Cytarabine DRUG

Treatment

Idarubicin DRUG

Treatment

Alisertib DRUG

Also known as: MLN8237

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Fathi AT, Wander SA, Blonquist TM, Brunner AM, Amrein PC, Supko J, Hermance NM, Manning AL, Sadrzadeh H, Ballen KK, Attar EC, Graubert TA, Hobbs G, Joseph C, Perry AM, Burke M, Silver R, Foster J, Bergeron M, Ramos AY, Som TT, Fishman KM, McGregor KL, Connolly C, Neuberg DS, Chen YB. Phase I study of the aurora A kinase inhibitor alisertib with induction chemotherapy in patients with acute myeloid leukemia. Haematologica. 2017 Apr;102(4):719-727. doi: 10.3324/haematol.2016.158394. Epub 2016 Dec 29.

  PMID: 28034990 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Idarubicin; MLN 8237

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Amir Fathi, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: January 30, 2013
• Study Start: April 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2016
• Last Updated: February 17, 2017

Record last verified: 2017-02

Locations

US (3)