UPCC 02407: Sirolimus in Combination With MEC in High Risk Myeloid Leukemias

Sponsor

Abramson Cancer Center of the University of Pennsylvania (Other)

Overall Status

Completed

CT.gov ID

NCT00780104

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Myeloid Leukemias AML Leukemia CML	Drug: Rapamycin, Mitoxantrone, Etoposide, Cytarabine Drug: Rapamycin + MEC	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 2007

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Jun 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rapamycin + MEC	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. Drug: 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.

Arm

Intervention/Treatment

Experimental: Rapamycin + MEC

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.

Drug: Rapamycin + MEC

Outcome Measures

Primary Outcome Measures

Assessment of biologic effects of rapamycin on mTOR targets such as p70 protein phosphorylation in leukemic cells [Study conclusion]

Secondary Outcome Measures

Safety of the sirolimus + MEC regimen [Study conclusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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