Sirolimus in Combination With MEC in High Risk Myeloid Leukemias

Leukemia Clinical Trial

— UPCC 02407  

Official title:

A Prospective Single Institution Pilot Study Evaluating the Pharmacokinetics of Sirolimus in Combination With MEC (Mitoxantrone + Etoposide + Cytarabine) in Patients With High Risk Leukemias

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00780104
• Other study ID #: UPCC 02407
• Status: Completed
• Phase: Phase 1
• Start date: July 2007
• Est. completion date: June 2010

Study information

• Verified date: July 2019
• Source: Abramson Cancer Center of the University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the side effects of sirolimus (rapamycin) given in combination with chemotherapy (Mitoxantrone + Etoposide + Cytarabine (MEC)) on high risk myeloid leukemias.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must have histologic evidence of advanced myeloid leukemias defined as one of the following: primary refractory non-M3 AML; relapsed non-M3 AML; secondary AML; intermediate or poor prognosis de novo AML in patients who are >= 60 years old

• >= 18 years of age

• ECOG performance status of 0, 1

• Able to consume oral medication

• Initial laboratory values: creatinine <= 2.0 mg/dL; total or direct bilirubin <= 1.5/dL; SGPT(ALT) <= 3xULN; negative pregnancy test for women with child-bearing potential

• Ejection fraction of >= 45%

Exclusion Criteria:

• Subjects with FAM B3

• Must not be receiving chemotherapy (except Hydroxyurea)

• Not receiving growth factors, except for erythropoietin

• Subjects with a "currently active" second malignancy other than non-melanoma skin cancers

• Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, MI within the last 6 months or uncontrolled cardiac arrhythmia

• Subjects taking diltiazem

• Subjects who require HIV protease inhibitors or those with AIDS-related illnesses

• No evidence of cerebellar dysfunction at baseline or during prior cytarabine therapy

• Not pregnant or breastfeeding

• Uncontrolled infection

• Subjects taking Carbamazepine, Rifabutin, Rifampin, Rifapentine, St. John's wort, Clarithromycin, Cyclosporine, Diltiazem, Erythromycin, Telithromycin, Verapamil, Tacrolimus

Related Conditions & MeSH terms

• AML
• CML
• Leukemia
• Leukemia, Myeloid
• Myeloid Leukemias

Intervention

Drug:
• Rapamycin, Mitoxantrone, Etoposide, Cytarabine
Rapamycin loading dose of 12 mg followed by a single daily dose for 8 days of 4 mg/day + MEC (Mitoxantrone 8 mg/m2/day IV, Etoposide 100 mg/m2/day IV and Cytarabine 1000 mg/m2 IV every 24 hours for 5 days. Starts after 4th dose of sirolimus.
• Rapamycin + MEC
Rapamycin loading dose of 12 mg followed by a single daily dose for 8 days of 4 mg/day + MEC (Mitoxantrone 8 mg/m2/day IV, Etoposide 100 mg/m2/day IV and Cytarabine 1000 mg/m2 IV every 24 hours for 5 days. Starts after 4th dose of sirolimus.

Locations

Country	Name	City	State
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abramson Cancer Center of the University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of biologic effects of rapamycin on mTOR targets such as p70 protein phosphorylation in leukemic cells		Study conclusion
Secondary	Safety of the sirolimus + MEC regimen		Study conclusion