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Everolimus MICE-regimen in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML1208)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier:
NCT01154439
First received: June 29, 2010
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: cytarabine
Drug: etoposide
Drug: everolimus
Drug: idarubicin
Drug: mitoxantrone hydrochloride
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:

Primary Outcome Measures:
  • Maximum-tolerated dose of everolimus [ Time Frame: At one year from study entry ] [ Designated as safety issue: Yes ]
    MTD of RAD given in combination with the MICE regimen


Secondary Outcome Measures:
  • Safety [ Time Frame: At one year from study entry ] [ Designated as safety issue: Yes ]
  • Complete remission rate [ Time Frame: At one year from study entry ] [ Designated as safety issue: No ]
    Complete remission rate (CR + CRi) following one or two induction courses.


Estimated Enrollment: 18
Study Start Date: October 2010
Estimated Study Completion Date: June 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: cytarabine
    Remission induction therapy: by short i.v. infusion on days 1 and 7. Consolidation therapy: by continuous infusion on days 1-5.
    Other Name: Mini-ICE regimen (idarubicin, cytarabine and etoposide).
    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.
    Other Name: Mini-ICE regimen (idarubicin, cytarabine and etoposide).
    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.

    Other Name: RAD001
    Drug: idarubicin
    Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.
    Other Name: Mini-ICE regimen (idarubicin, cytarabine and etoposide).
    Drug: mitoxantrone hydrochloride
    Remission induction therapy: by short i.v. infusion on days 1, 3 and 5
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

Ages Eligible for Study:   61 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154439

Locations
Italy
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, Italy, 00100
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Rome, Italy, 00133
Sponsors and Collaborators
Gruppo Italiano Malattie EMatologiche dell'Adulto
Investigators
Principal Investigator: Sergio Amadori, MD Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  More Information

Additional Information:
No publications provided

Responsible Party: Gruppo Italiano Malattie EMatologiche dell'Adulto
ClinicalTrials.gov Identifier: NCT01154439     History of Changes
Other Study ID Numbers: AML1208, GIMEMA-AML1208, 2008-007666-28
Study First Received: June 29, 2010
Last Updated: March 20, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by Gruppo Italiano Malattie EMatologiche dell'Adulto:
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)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Etoposide
Etoposide phosphate
Everolimus
Idarubicin
Mitoxantrone
Sirolimus
Analgesics
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Antiviral Agents
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014