Sirolimus in Combination With MEC in High Risk Myeloid Leukemias - Full Text View

Sponsored by:	University of Pennsylvania
Information provided by:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00780104

Purpose

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	Intervention	Phase
Myeloid Leukemias AML Leukemia CML	Drug: Rapamycin, Mitoxantrone, Etoposide, Cytarabine Drug: Rapamycin + MEC	Phase I

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cytarabine hydrochloride Etoposide Sirolimus Mitoxantrone Mitoxantrone hydrochloride Etoposide phosphate Cytarabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
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

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

Assessment of biologic effects of rapamycin on mTOR targets such as p70 protein phosphorylation in leukemic cells [ Time Frame: Study conclusion ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety of the sirolimus + MEC regimen [ Time Frame: Study conclusion ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	15
Study Start Date:	July 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Rapamycin + MEC: Experimental	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.

Arms

Assigned Interventions

Rapamycin + MEC: Experimental

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00780104

Contacts

Contact: Doris Shank

215-662-4712

Doris.Shank@uphs.upenn.edu

Locations

United States, Pennsylvania
University of Pennsylvania Abramson Cancer Center	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Doris Shank 215-662-4712 Doris.Shank@uphs.upenn.edu

Sponsors and Collaborators

University of Pennsylvania

More Information

No publications provided

Responsible Party:	University of Pennsylvania Abramson Cancer Center ( Selina Luger, M.D. )
Study ID Numbers:	UPCC 02407
Study First Received:	October 24, 2008
Last Updated:	October 24, 2008
ClinicalTrials.gov Identifier:	NCT00780104 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:

Advanced myeloid leukemias
AML
Leukemia
Relapsed myeloid leukemias

Refractory myeloid leukemias
MEC
Rapamycin
Sirolimus

Study placed in the following topic categories:

Sirolimus
Antimetabolites
Immunologic Factors
Clotrimazole
Miconazole
Tioconazole
Leukemia, Myeloid
Etoposide phosphate
Antiviral Agents
Immunosuppressive Agents

Anti-Bacterial Agents
Leukemia
Antifungal Agents
Peripheral Nervous System Agents
Mitoxantrone
Analgesics
Etoposide
Antineoplastic Agents, Phytogenic
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Sirolimus
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Etoposide phosphate
Anti-Bacterial Agents
Leukemia
Sensory System Agents
Antifungal Agents

Therapeutic Uses
Analgesics
Etoposide
Cytarabine
Neoplasms by Histologic Type
Leukemia, Myeloid
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Mitoxantrone
Peripheral Nervous System Agents
Antineoplastic Agents, Phytogenic
Central Nervous System Agents

ClinicalTrials.gov processed this record on May 07, 2009