Pilot Trial of Sirolimus/MEC in High Risk Acute Myelogenous Leukemia (AML)

NCT01184898 | Completed Results DMC

• 3 other identifiers: 10D.212009-42JT 1520
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the addition of Sirolimus (rapamycin) to standard chemotherapy for the treatment of patients with high risk acute myelogenous leukemia (AML). Cancer cells taken from the patients will be studied in the laboratory to see if rapamycin is affecting the mTOR pathway in the cells and if this effect is correlated with how well patients respond to the therapy.

Conditions

AML

Keywords

AML; mTOR; rapamycin

Outcome Measures

Primary Outcomes (1)

• Association Between the Magnitude of mTOR Target Inhibition Post-treatment in Leukemic Blasts and Clinical Response in Patients With High Risk AML Treated With Sirolimus MEC

  Percent change compared between response groups (responder vs nonresponder). This outcome measure only includes patients who survived to outcome assessment.

  From pre- to post-treatment

Secondary Outcomes (3)

• Complete Response

  Within one week of peripheral count recovery but no later than day 42

• Complete Response in the Absence of Platelet Recovery

  Within one week of peripheral count recovery but no later than day 42

• Partial Response

  Within one week of peripheral count recovery but no later than day 42

Study Arms (1)

Sirolimus and MEC

EXPERIMENTAL

Sirolimus and MEC (Mitoxantrone, Etoposide, and Cytarabine)

Drug: Sirolimus; Drug: Mitoxantrone; Drug: Etoposide; Drug: Cytarabine

Interventions

Sirolimus DRUG

Sirolimus, by mouth, will be given as a 12mg loading dose followed by 8 daily doses of 4mg/day.

Also known as: Rapamycin

Sirolimus and MEC

Mitoxantrone DRUG

Mitoxantrone 8mg/m2/day IV

Also known as: Mitozantrone, Novantrone

Sirolimus and MEC

Etoposide DRUG

100 mg/m2/day IV

Also known as: Etoposide phosphate, VP-16, Etopophos

Sirolimus and MEC

Cytarabine DRUG

1000mg/m2/day IV every 24 hours for 5 days

Also known as: Cytosine arabinoside, Cytosar-U, Depocyt, ara-C

Sirolimus and MEC

Eligibility Criteria

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

You may qualify if:

• Patients must have histologic evidence of high risk acute myeloid leukemia defined as one of the following:
• Primary refractory non-M3 AML (i) Residual leukemia after a minimum of 2 prior courses of chemotherapy (Same or different) (ii) Evidence of leukemia after a nadir bone marrow biopsy demonstrates no evidence of residual leukemia.
• Relapsed non-M3 AML
• Any non-M3 AML age \>60 with no evidence of favorable karyotype (stratum 2 ONLY), defined by presence of t(8;21)(q22;q22) \[AML1-ETO\], inv16(p13;q22), or t(16;16)(p13;q22) \[CBF;MYH11\] by cytogenetics, FISH, or RT-PCR
• Secondary AML (from antecedent hematologic malignancy or following therapy with radiation or chemotherapy for another disease) with no evidence of favorable karyotype (stratum 2 ONLY), defined by presence of t(8;21)(q22;q22) \[AML1-ETO\], inv16(p13;q22), or t(16;16)(p13;q22) \[CBF;MYH11\] by cytogenetics, FISH, or RT-PCR
• Age \> or = 18
• ECOG = 0 or 1

You may not qualify if:

• Subjects with FAB M3 (t(15;17)(q22;q21)\[PML-RAR\]) are not eligible
• Subjects taking the following are not eligible:
• Carbamazepine (e.g., Tegretol)
• Rifabutin (e.g., Mycobutin) or
• Rifampin (e.g., Rifadin)
• Rifapentine (e.g., Priftin)
• St. John's wort
• Clarithromycin (e.g., Biaxin)
• Cyclosporine (e.g. Neoral or Sandimmune)
• Diltiazem (e.g., Cardizem)
• Erythromycin (e.g., Akne-Mycin, Ery-Tab)
• Itraconazole (e.g., Sporanox)
• Ketoconazole (e.g., Nizoral)
• Telithromycin (e.g., Ketek)
• Verapamil (e.g., Calan SR, Isoptin, Verelan)

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• University of Pennsylvania: collaborator

Study Sites (2)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Interventions

Sirolimus; Mitoxantrone; Etoposide; etoposide phosphate; Cytarabine

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Quinones; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Margaret Kasner, MD
• Organization: Thomas Jefferson University

Margaret.Kasner@jefferson.edu

215-955-8874

Study Officials

• Margaret Kasner, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2010
• First Posted: August 19, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2012
• Study Completion: February 1, 2016
• Last Updated: May 31, 2025
• Results First Posted: August 27, 2014

Record last verified: 2025-05

Locations

US (2)