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

NCT01154439 | Completed Phase 1

• 3 other identifiers: AML1208GIMEMA-AML12082008-007666-28
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

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.

Conditions

Leukemia

Keywords

secondary acute myeloid leukemia; untreated adult acute myeloid leukemia; adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22)

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose of everolimus

  MTD of RAD given in combination with the MICE regimen

  At one year from study entry

Secondary Outcomes (2)

• Safety

  At one year from study entry

• Complete remission rate

  At one year from study entry

Study Arms (1)

Everolimus

EXPERIMENTAL

Everolimus mice-regimen

Drug: cytarabine; Drug: etoposide; Drug: everolimus; Drug: idarubicin; Drug: mitoxantrone hydrochloride

Interventions

cytarabine DRUG

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

Also known as: Mini-ICE regimen (idarubicin, cytarabine and etoposide).

Everolimus

etoposide DRUG

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

Also known as: Mini-ICE regimen (idarubicin, cytarabine and etoposide).

Everolimus

everolimus 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.

Also known as: RAD001

Everolimus

idarubicin DRUG

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

Also known as: Mini-ICE regimen (idarubicin, cytarabine and etoposide).

Everolimus

mitoxantrone hydrochloride DRUG

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

Everolimus

Eligibility Criteria

• Age: 61 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Gruppo Italiano Malattie EMatologiche dell'Adulto: lead

Study Sites (5)

Ematologia con trapianto- AOU Policlinico Consorziale di Bari

Bari, Italy

Location

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

Napoli, Italy

Location

Università La Sapienza

Roma, 00100, Italy

Location

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

Roma, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Rome, 00133, Italy

Location

Related Links

• GIMEMA Foundation Website

MeSH Terms

Conditions

Leukemia; Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Congenital Abnormalities

Interventions

Cytarabine; Idarubicin; Etoposide; Everolimus; Mitoxantrone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Sirolimus; Macrolides; Lactones; Anthraquinones; Anthrones; Anthracenes; Quinones

Study Officials

• Sergio Amadori, MD

  Azienda Ospedaliera Universitaria Policlinico Tor Vergata

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2010
• First Posted: June 30, 2010
• Study Start: October 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: September 15, 2015
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5)