Everolimus MICE-regimen in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT ID: NCT01154439

Last Updated: 2022-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2015-09-15

Brief 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.

Detailed 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.

Conditions

Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus

Everolimus mice-regimen

Group Type: EXPERIMENTAL

cytarabine

Intervention Type: DRUG

Remission induction therapy: by short i.v. infusion on days 1 and 7. Consolidation therapy: by continuous infusion on days 1-5.

etoposide

Intervention Type: DRUG

Remission induction therapy: by short i.v. infusion, on days 1-7. Consolidation therapy: by short i.v. infusion, on days 1-5.

everolimus

Intervention Type: DRUG

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

Intervention Type: DRUG

Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.

mitoxantrone hydrochloride

Intervention Type: DRUG

Remission induction therapy: by short i.v. infusion on days 1, 3 and 5

Interventions

cytarabine

Remission induction therapy: by short i.v. infusion on days 1 and 7. Consolidation therapy: by continuous infusion on days 1-5.

Intervention Type: DRUG

etoposide

Remission induction therapy: by short i.v. infusion, on days 1-7. Consolidation therapy: by short i.v. infusion, on days 1-5.

Intervention Type: DRUG

everolimus

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.

Intervention Type: DRUG

idarubicin

Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.

Intervention Type: DRUG

mitoxantrone hydrochloride

Remission induction therapy: by short i.v. infusion on days 1, 3 and 5

Intervention Type: DRUG

Other Intervention Names

Mini-ICE regimen (idarubicin, cytarabine and etoposide).; Mini-ICE regimen (idarubicin, cytarabine and etoposide).; RAD001; Mini-ICE regimen (idarubicin, cytarabine and etoposide).

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 61 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gruppo Italiano Malattie EMatologiche dell'Adulto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergio Amadori, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Locations

Ematologia con trapianto- AOU Policlinico Consorziale di Bari

Bari, , Italy

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia

Napoli, , Italy

Università La Sapienza

Roma, , Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia

Roma, , Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, , Italy

Countries

Italy

Related Links

http://www.gimema.it

GIMEMA Foundation Website

Other Identifiers

GIMEMA-AML1208

Identifier Type: OTHER

Identifier Source: secondary_id

2008-007666-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AML1208

Identifier Type: -

Identifier Source: org_study_id