Overview

This trial is active, not recruiting.

Condition leukemia
Treatments cytarabine, etoposide, everolimus, idarubicin, mitoxantrone hydrochloride
Phase phase 1
Targets mTOR, FKBP-12
Sponsor Gruppo Italiano Malattie EMatologiche dell'Adulto
Start date October 2010
End date May 2013
Trial size 18 participants
Trial identifier NCT01154439, 2008-007666-28, AML1208, GIMEMA-AML1208

Summary

RATIONALE: Drugs used in chemotherapy, such as mitoxantrone hydrochloride, cytarabine, etoposide, and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Giving everolimus together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with mitoxantrone hydrochloride, cytarabine, etoposide, and idarubicin in treating older patients with newly diagnosed acute myeloid leukemia.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Everolimus mice-regimen
cytarabine Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Remission induction therapy: by short i.v. infusion on days 1 and 7. Consolidation therapy: by continuous infusion on days 1-5.
etoposide Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Remission induction therapy: by short i.v. infusion, on days 1-7. Consolidation therapy: by short i.v. infusion, on days 1-5.
everolimus RAD001
Remission induction therapy: test dose once a day by mouth, on days 1-21 (21 days). Consolidation therapy: dose as defined by the cohort once a day by mouth, on days 1-10.
idarubicin Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.
mitoxantrone hydrochloride
Remission induction therapy: by short i.v. infusion on days 1, 3 and 5

Primary Outcomes

Measure
Maximum-tolerated dose of everolimus
time frame: At one year from study entry

Secondary Outcomes

Measure
Safety
time frame: At one year from study entry
Complete remission rate
time frame: At one year from study entry

Eligibility Criteria

Male or female participants from 61 years up to 75 years old.

DISEASE CHARACTERISTICS: - Newly diagnosed acute myeloid leukemia (AML) (unequivocal) according to WHO diagnostic criteria (at least 20% blasts in the bone marrow), with FAB classification other than M3 (acute promyelocytic leukemia), and documented by bone marrow aspiration (or biopsy in case of dry tap) - Previously untreated primary or secondary AML (including AML following antecedent myelodysplasia) - No blast transformation of chronic myeloid leukemia or other myeloproliferative disorders - No active CNS leukemia PATIENT CHARACTERISTICS: - WHO performance status 0-2 - Total serum bilirubin < 2 times upper limit of normal (ULN) - Serum creatinine < 2 times ULN - ALT/AST ≤ 3 times ULN (unless due to organ leukemic involvement) - LVEF ≥ 50% by echocardiogram - No other concurrent active malignancy - No active uncontrolled infection - No known active hepatitis B or C or HIV positivity - No active heart disease including myocardial infarction within the past 3 months, symptomatic coronary artery disease, cardiac arrhythmias not controlled by medications, or uncontrolled congestive heart failure - No medical condition that, in the opinion of the investigator, places the patient at an unacceptably high risk for toxicities - No other known condition (e.g., familial, sociological, or geographical) or behavior (including drug dependence or abuse, psychological or psychiatric illness) that, in the opinion of the investigator, would make the patient a poor candidate for the trial - No known hypersensitivity to everolimus, other rapamycins (e.g., sirolimus or temsirolimus), or to its excipients PRIOR CONCURRENT THERAPY: - No prior standard or investigational chemotherapy for acute myeloid leukemia or myelodysplasia (including everolimus or other mTOR inhibitors) - Prior hydroxyurea allowed (up to a maximum of 14 days) to control peripheral blood leukemic cell counts - No prior enrollment in this trial - No other concurrent anti-leukemia agents, investigational agents, or biological agents

Additional Information

Official title A Phase I Study Investigating the Combination of RAD001 With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Principal investigator Sergio Amadori, MD
Description OBJECTIVES: Primary - To determine the maximum-tolerated dose of everolimus in combination with standard remission-induction therapy comprising mitoxantrone hydrochloride, cytarabine, and etoposide (MICE-regimen) followed by consolidation therapy comprising idarubicin, cytarabine, and etoposide in older patients with newly diagnosed acute myeloid leukemia. Secondary - To determine the safety profile of this regimen in these patients. - To determine the anti-leukemic activity (complete remission rate [complete remission and complete remission with incomplete blood count recovery]) following one or two induction courses. OUTLINE: This is a multicenter, dose-escalation study of everolimus. - Standard remission-induction therapy: Patients receive mitoxantrone hydrochloride IV over 30 minutes on days 1, 3, and 5; cytarabine IV continuously on days 1-7; etoposide IV over 1 hour on days 1-3; and oral everolimus once a day on days 1-21. Patients with partial remission (PR) receive a second induction course, beginning 7-17 days after completion of induction course 1. Patients with complete remission or complete remission with incomplete blood count recovery (CR/CRi) after induction therapy proceed to consolidation therapy; patients who have failed to achieve PR after induction course 1 or a CR/CRi after induction course 2 are removed from study. - Consolidation therapy: Beginning within 3 weeks from CR/CRi documentation, patients receive idarubicin IV over 30 minutes on days 1, 3, and 5; cytarabine IV continuously on days 1-5; etoposide IV over 1 hour on days 1-3; and oral everolimus once a day on days 1-10. Patients may receive another course of the consolidation therapy, beginning at least 4 weeks after initiation of consolidation therapy course 1. After completion of study treatment, patients are followed up once a month for 1 year, every 3 months for 1 year, and then periodically thereafter.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Gruppo Italiano Malattie EMatologiche dell'Adulto.