Official Title: “A Dose Escalation Phase I/II Study of Lovastatin With High-Dose Cytarabine for Patients With Refractory or Relapsed Acute Myeloid Leukemia”

The purpose of this study is to test the safety and effectiveness of combining a drug known as Lovastatin to the chemotherapy drug cytarabine.

Lovastatin is currently used to lower blood cholesterol levels and lab data suggests that it increases the anti-leukemia activity of cytarabine. This research is being done because high doses of cytarabine induce remissions in only about 25% of patients with acute myeloid leukemia.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment

Study Primary Completion Date: June 2011

Intervention(s) in this Clinical Trial

• Drug: Lovastatin and Cytarabine
  • Cytarabine dosage: 3.0 g/m2 IV over 3 hours every 12 hours on days 3-7. Lovastatin dosage: The first dose level will be lovastatin at 0.5 mg/kg/day. After each patient reaches day 14 subsequent patients will be treated at incrementally increasing doses that are 1 mg/kg/day, 2 mg/kg/day, 4 mg/kg/day, 8 mg/kg/day, 12 mg/kg/day, 18 mg/kg/day, and 24 mg/kg/day. If MTD is not reached at this dose of 24 mg/kg/day further dose escalations will occur with a 33% increase in dose at each level rounded to the nearest mg/kg/day.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • The subject will receive high dose cytarabine as well as lovastatin. The subject will take doses of lovastatin twice a day, about 12 hours apart. On the third day, the subject will begin high-dose cytarabine IV over 3 hours, twice a day, starting 1 hour after the lovastatin dose for 5 days.

Primary Measures

• Complete remission rate
  • Time Frame: 5 weeks
    Safety Issue?: No

Inclusion Criteria:

• Patients with primary refractory AML (that is no prior remission). Patients who have greater than 10% AML blasts in the bone marrow or blood upon recovery from two cycles of standard cytarabine- and anthracycline-based induction chemotherapy are eligible.
• Patients who have received etoposide and/or 6-thioguanine during remission induction will be eligible.
• Patients with relapsed AML. Patients must have had a documented remission lasting > 30 days at some point during their prior therapy. Their current relapse must be untreated. Relapse is defined as the presence of greater than 10% AML blasts in the bone marrow or blood after having had a documented remission.
• Patients who have received a high-dose cytarabine containing regimen (>2 g/m2/dose) within 3 months prior to registration on this protocol are not eligible.
• No active CNS involvement. A lumbar puncture prior to treatment is not required and should not be performed in the absence of significant CNS symptoms or signs.
• Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.

Exclusion Criteria:

• Although NOT considered formal Exclusion Criteria, study physicians are strongly encouraged as part of this decision-making process to recognize that the following may increase the risks to a subject entering this protocol:
• Other serious illnesses which would limit survival to <2 years, or a psychiatric condition which would prevent compliance with treatment or informed consent.
• Performance Status > 2.
• Uncontrolled or severe cardiovascular disease, diabetes, pulmonary disease, or infection, which in the opinion of the treating physician, would make this protocol treatment unreasonably hazardous for the patient.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and considered by their physician to be at less than 30% risk of relapse within one year.
• Patients who have received any investigational agent within the prior 4 weeks.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Iowa

Overall Clinical Trial Officials and Contacts

Raymond Hohl, MD Principal Investigator University of Iowa  

Overall Contact: Raymond Hohl, MD 319-356-8110 raymond-hohl@uiowa.edu

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00583102

Study ID Number: 200104050

ClinicalTrials.gov Identifier: NCT00583102

Health Authority: United States: Food and Drug Administration