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

Information source: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Leukemia

Intervention: cytarabine (Drug); etoposide (Drug); everolimus (Drug); idarubicin (Drug); mitoxantrone hydrochloride (Drug)

Phase: Phase 1

Status: Active, not recruiting

Sponsored by: Gruppo Italiano Malattie EMatologiche dell'Adulto

Official(s) and/or principal investigator(s):
Sergio Amadori, MD, Principal Investigator, Affiliation: Azienda Ospedaliera Universitaria Policlinico Tor Vergata

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.

Clinical Details

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)

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Maximum-tolerated dose of everolimus

Secondary outcome:

Safety

Complete remission rate

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.

Eligibility

Minimum age: 61 Years. Maximum age: 75 Years. Gender(s): Both.

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

Locations and Contacts

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 degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia, Roma, Italy

Università La Sapienza, Roma 00100, Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata, Rome 00133, Italy

Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

GIMEMA Foundation Website

Starting date: October 2010
Last updated: July 9, 2015

Page last updated: August 23, 2015

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