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

This study is currently recruiting participants. (see Contacts and Locations)
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
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 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
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Lovastatin
Anti-Infective Agents
Anticholesteremic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Immunologic Factors
Immunosuppressive Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014