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

NCT00583102 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: 200104050
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; AML; Lovastatin; Cytarabine

Outcome Measures

Primary Outcomes (1)

• Complete Remission Rate

  The primary study end point will be complete remission rate. Complete Remission (CR): Complete remission is defined as the presence of all of the following: Peripheral Blood Counts (sustained \> 30 days) * Absolute neutrophil count ³1500/ml. * Platelet count ³100,000/ml. * No leukemic blasts in the peripheral blood. * Transfusion independent for red cells and platelets. Bone Marrow * Cellularity \>20% with maturation of all cell lines. * No Auer rods. * \<5% blast cells. No extramedullary leukemia (such as CNS or soft tissue involvement). OR Complete Response with Incomplete Platelet Recovery (CRp): CRp satisfies all CR criteria except platelets \< 100,000/µL. Partial Remission (PR): Must meet all criteria of a CR except that the bone marrow may contain 5-24% blasts. Treatment Failure: Failure to achieve a CR.

  5 weeks

Study Arms (1)

Lovastatin followed by Cytarabine

EXPERIMENTAL

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: Cytarabine; Drug: Lovastatin

Interventions

Cytarabine DRUG

Cytarabine dosage: 3.0 g/m2 IV over 3 hours every 12 hours on days 3-7.

Also known as: CYTOSAR-U, Depocyt

Lovastatin followed by Cytarabine

Lovastatin DRUG

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.

Also known as: Mevacor, Altoprev

Lovastatin followed by Cytarabine

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Lovastatin

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; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Trial terminated early due to slow accrual. PI left the institution.

Results Point of Contact

• Title: Raymond Hohl, MD
• Organization: University of Iowa

rhohl@pennstatehealth.psu.edu

319-356-8110

Study Officials

• Raymond Hohl, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Professor Emeritus

Study Record Dates

• First Submitted: December 20, 2007
• First Posted: December 31, 2007
• Study Start: June 1, 2001
• Primary Completion: February 1, 2013
• Study Completion: June 1, 2013
• Last Updated: January 5, 2018
• Results First Posted: January 5, 2018

Record last verified: 2017-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)