Sirolimus in Combination With MEC in High Risk Myeloid Leukemias (UPCC 02407)
Primary Purpose
Myeloid Leukemias, AML, Leukemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Rapamycin, Mitoxantrone, Etoposide, Cytarabine
Rapamycin + MEC
Sponsored by

About this trial
This is an interventional treatment trial for Myeloid Leukemias focused on measuring Advanced myeloid leukemias, AML, Leukemia, Relapsed myeloid leukemias, Refractory myeloid leukemias, MEC, Rapamycin, Sirolimus
Eligibility Criteria
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
Sites / Locations
- University of Pennsylvania Abramson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rapamycin + MEC
Arm Description
Outcomes
Primary Outcome Measures
Assessment of biologic effects of rapamycin on mTOR targets such as p70 protein phosphorylation in leukemic cells
Secondary Outcome Measures
Safety of the sirolimus + MEC regimen
Full Information
NCT ID
NCT00780104
First Posted
October 24, 2008
Last Updated
July 10, 2019
Sponsor
Abramson Cancer Center at Penn Medicine
1. Study Identification
Unique Protocol Identification Number
NCT00780104
Brief Title
Sirolimus in Combination With MEC in High Risk Myeloid Leukemias
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloid Leukemias, AML, Leukemia, CML
Keywords
Advanced myeloid leukemias, AML, Leukemia, Relapsed myeloid leukemias, Refractory myeloid leukemias, MEC, Rapamycin, Sirolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rapamycin + MEC
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Rapamycin, Mitoxantrone, Etoposide, Cytarabine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rapamycin + MEC
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assessment of biologic effects of rapamycin on mTOR targets such as p70 protein phosphorylation in leukemic cells
Time Frame
Study conclusion
Secondary Outcome Measure Information:
Title
Safety of the sirolimus + MEC regimen
Time Frame
Study conclusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of Pennsylvania Abramson Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Sirolimus in Combination With MEC in High Risk Myeloid Leukemias
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