Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT01822015 | Completed Early Phase 1 DMC FDA Drug

• 3 other identifiers: 12D.5882012-55JT 3038
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies sirolimus, idarubicin, and cytarabine in treating patients with newly diagnosed acute myeloid leukemia. Sirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as idarubicin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving sirolimus together with idarubicin and cytarabine may kill more cancer cells.

Conditions

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Change in measurement of mTOR activation paired with mTOR target inhibition

  The association between mTOR response and clinical response (complete or partial response) will be evaluated using the two-sided Fisher's exact test with alpha 0.05.

  Baseline to day 4

Secondary Outcomes (4)

• Overall survival

  1 year, 2 years, 5 years

• Progression free survival

  1 year, 2 years, 5 years

• Incidence of toxicities, graded according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) 4.0 guidelines

  Up to 45 days

• Response defined as patients achieving a complete remission (CR), complete response in absence of total platelet recovery (CRp), or partial remission (PR)

  Up to 5 years

Study Arms (1)

Treatment (sirolimus, idarubicin, cytarabine)

EXPERIMENTAL

Patients receive sirolimus PO QD on days 1-10, idarubicin IV over 3-5 minutes on days 4-6, and cytarabine IV continuously over 24 hours on days 4-10.

Drug: Sirolimus; Drug: Idarubicin; Drug: Cytarabine

Interventions

Sirolimus DRUG

Given PO

Also known as: rapamycin, Rapamune

Treatment (sirolimus, idarubicin, cytarabine)

Idarubicin DRUG

Given IV

Also known as: 4-demethoxydaunorubicin, Zavedos, Idamycin

Treatment (sirolimus, idarubicin, cytarabine)

Cytarabine DRUG

Given IV

Also known as: cytosine arabinoside, Cytosar-U, Depocyt, Ara-C, Arabinofuranosyl Cytidine

Treatment (sirolimus, idarubicin, cytarabine)

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 newly diagnosed acute myeloid leukemia (non-M3 AML) as documented by the presence of \>20% myeloid blasts in the bone marrow
• Subjects must be 18 years of age and \<= 60
• Subjects must have an ECOG performance status of 2 or less. (see attachment 1).
• Subjects must have a life expectancy of at least 4 weeks.
• Subjects must be able to consume oral medication.
• Required initial laboratory values: Creatinine 2.0mg/dL; total or direct bilirubin 1.5mg/dL; SGPT(ALT) 3xULN (if not due to the leukemia itself); negative pregnancy test for women with child-bearing potential.
• Patients must be able to sign consent and be willing and able to comply with scheduled visits, treatment plan and laboratory testing.
• Subjects must have a left ventricular ejection fraction (LVEF) of \>/= 45%.

You may not qualify if:

• Subjects with APL - FAB M3 (t(15;17)(q22;q21)\[PML-RAR\] are not eligible
• Subjects must not have received any chemotherapeutic agents for the AML (except Hydroxyurea). Intrathecal ARA-C and intrathecal methotrexate are permissible (as they are not systemic and only isolated to the central nervous system).
• Subjects must not be receiving growth factors, except for erythropoietin.
• Subjects with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible.
• Subjects with uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the past 6 months or serious uncontrolled cardiac arrhythmia are not eligible.
• Subjects taking the following are not eligible:
• Carbamazepine (e.g., Tegretol)
• Rifabutin (e.g., Mycobutin)
• 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)

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

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Related Links

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

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

Sirolimus; Idarubicin; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Margaret Kasner, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: April 1, 2013
• Study Start: March 15, 2013
• Primary Completion: December 12, 2019
• Study Completion: December 12, 2019
• Last Updated: April 29, 2025

Record last verified: 2025-04

Locations

US (1)