Dose Escalation Phase I/II Study of Lovastatin With High-Dose Cytarabine for Refractory or Relapsed AML

This study is currently recruiting participants.
Verified December 2010 by University of Iowa
Sponsor:
Information provided by:
University of Iowa
ClinicalTrials.gov Identifier:
NCT00583102
First received: December 20, 2007
Last updated: December 20, 2010
Last verified: December 2010
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Lovastatin and Cytarabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Dose Escalation Phase I/II Study of Lovastatin With High-Dose Cytarabine for Patients With Refractory or Relapsed Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Complete remission rate [ Time Frame: 5 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: June 2001
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00583102

Contacts
Contact: Raymond Hohl, MD 319-356-8110 raymond-hohl@uiowa.edu
Contact: Karen Parrott, RN 319-353-6347 karen-parrott@uiowa.edu

Locations
United States, Iowa
Holden Comprehensive Cancer Center Recruiting
Iowa City, Iowa, United States, 52242
Contact: Raymond Hohl, MD    319-356-8110    raymond-hohl@uiowa.edu   
Contact: Karen Parrott, RN    319-353-6347    karen-parrott@uiowa.edu   
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: Raymond Hohl, MD University of Iowa
  More Information

No publications provided

Responsible Party: Raymond Hohl, MD, University of Iowa
ClinicalTrials.gov Identifier: NCT00583102     History of Changes
Other Study ID Numbers: 200104050
Study First Received: December 20, 2007
Last Updated: December 20, 2010
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Iowa:
Acute Myeloid Leukemia
AML
Lovastatin
Cytarabine

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Lovastatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Enzyme Inhibitors
Lipid Regulating Agents

ClinicalTrials.gov processed this record on April 23, 2014