NCT00583102

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

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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: University of Iowa · Academic / Other
• Sex: All
• Age: 18 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

The rationale for combining lovastatin with cytosine arabinoside (HiDAC) in this trial is based on a study in press in Leukemia Research. This study demonstrated that there are synergistic interactions between cytosine arabinoside and lovastatin against human leukemia cell lines. In particular, this synergistic activity was observed in MTT assay. Given that there is such synergistic interaction in vitro it is reasonable to determine whether such interaction occurs in vivo. The proposed trial thus uses standard doses of HiDAC with incrementally increasing dose of lovastatin. This particular trial will follow an accelerated titration for lovastatin. The first dose level will be lovastatin at 0.5 mg/kg/day, divided into two daily PO doses given Q 12 hours on Days 1 -7 for a total of 14 doses. Doses should be rounded to the nearest 20 mg. After each subject reaches day 14, subsequent subjects 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, with all doses divided into two daily PO doses given Q 12 hours on Days 1 - 7 for a total of 14. If MTD is not reached at the 24 mg/kg/day dose level, further dose escalations will occur with a 33% increase in dose at each level, rounded to the nearest 20 mg/kg/day.

Conditions

• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Cytarabine	Cytarabine dosage: 3.0 g/m2 IV over 3 hours every 12 hours on days 3-7.
DRUG	Lovastatin	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.

Timeline

• Start date: 2001-06-01
• Primary completion: 2013-02-01
• Completion: 2013-06-01
• First posted: 2007-12-31
• Last updated: 2018-01-05
• Results posted: 2018-01-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study