Everolimus MICE-regimen in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Information source: Gruppo Italiano Malattie EMatologiche dell'Adulto
Information obtained from ClinicalTrials.gov on February 07, 2013
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
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
Paola FAZI, Dr., Email: email@example.com
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
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.
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
Complete remission rate
- 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
- 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
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.
Minimum age: 61 Years.
Maximum age: 75 Years.
- 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
- No blast transformation of chronic myeloid leukemia or other myeloproliferative
- No active CNS leukemia
- 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
- 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
Locations and Contacts
Paola FAZI, Dr., Email: firstname.lastname@example.org
Ematologia con trapianto- AOU Policlinico Consorziale di Bari, Bari, Italy; Recruiting
Giorgina SPECCHIA, Pr.
Domenico PASTORE, Dr., Sub-Investigator
Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia, Napoli, Italy; Recruiting
Fabrizio PANE, Pr.
Fabrizio PANE, Pr., Principal Investigator
Università La Sapienza, Roma 00100, Italy; Not yet recruiting
Giuliana ALIMENA, Pr., Principal Investigator
Massimo BRECCIA, Dr., Sub-Investigator
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia, Roma, Italy; Recruiting
Roberto FOA', Pr.
Cluadio CARTONI, Dr., Sub-Investigator
Roberto FOA', Pr., Principal Investigator
Azienda Ospedaliera Universitaria Policlinico Tor Vergata, Rome 00133, Italy; Recruiting
Sergio AMADORI, Pr.
Sergio AMADORI, Pr., Principal Investigator
Adriano VENDITTI, Pr., Sub-Investigator
Clinical trial summary from the National Cancer Institute's PDQ® database
GIMEMA Foundation Website
Starting date: October 2010
Last updated: May 7, 2012