Everolimus, Cytarabine, and Daunorubicin in Treating Patients With Relapsed Acute Myeloid Leukemia

Leukemia Clinical Trial

Official title:

Phase I Study Evaluating the Chemosensitizing Effect of Everolimus Administered With Cytarabine and Daunorubicin in Patients With Acute Myeloid Leukemia in Relapse

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00544999
• Other study ID #: CDR0000564068
• Secondary ID: IRLMS-GOELAMS-RA
• Status: Recruiting
• Phase: Phase 1
• First received: October 13, 2007
• Last updated: September 16, 2013
• Start date: September 2007

Study information

• Verified date: July 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Everolimus may help cytarabine and daunorubicin work better by making cancer cells more sensitive to chemotherapy. Giving everolimus together with cytarabine and daunorubicin may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with cytarabine and daunorubicin in treating patients with relapsed acute myeloid leukemia.

Description:

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of everolimus.

• Determine the toxicity of this regimen.

Secondary

• Assess the activation of PI3K/AKT and mTORC 1 in leukemic blasts.

• Evaluate the pharmacokinetics of everolimus at different concentrations.

OUTLINE: This is a multicenter study.

Patients receive primary induction therapy comprising daunorubicin hydrochloride IV on days 1-3, cytarabine IV over 24 hours on day 1, and oral everolimus on days 1 and 7. Patients with more than 5% blasts on day 15 receive a second induction course comprising daunorubicin hydrochloride IV on days 17 and 18 and cytarabine IV twice daily on days 17-20.

After completion of study therapy, patients are followed for 3 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Diagnosis of de novo or secondary acute myeloid leukemia meeting the following criterion:

• Relapse > 1 year after obtaining complete remission (any prior treatment allowed)

Exclusion criteria:

• Philadelphia chromosome-positive disease in blast crisis

• FAB M3, M6, or M7 disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Life expectancy = 4 weeks

• Transaminases = 5 times normal

• Creatinine = 2 times normal

• Bilirubin = 3 times normal (except if visceral involvement present)

• Alkaline phosphatase or gamma-glutamyltransferase = 5 times normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients of must use effective contraception during and for = 28 days after completion of study therapy

Exclusion criteria:

• FEV1 < 30%

• Active uncontrolled or viral pulmonary infection

• Serious psychiatric disorders not related to leukemia or any condition that would prohibit comprehension of the study

• HIV-positive

• Other concurrent malignancy except noninvasive skin cancer or carcinoma in situ

• Patients who are incarcerated or under supervision or trusteeship

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

Exclusion criteria:

• Prior experimental medication within the past 4 weeks

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• cytarabine

• daunorubicin hydrochloride

• everolimus

Other:
• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
France	Hopital Cochin	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Recherche Clinique sur les Cancers et le Sang

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of everolimus			Yes
Primary	Toxicity			Yes
Secondary	Activation of PI3K/AKT and mTORC 1 in leukemic blasts			No
Secondary	Pharmacokinetics of everolimus			No