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

Primary Purpose

Leukemia

Status
Completed
Phase
Phase 1
Locations
Italy
Study Type
Interventional
Intervention
cytarabine
etoposide
everolimus
idarubicin
mitoxantrone hydrochloride
Sponsored by
Gruppo Italiano Malattie EMatologiche dell'Adulto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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)

Eligibility Criteria

61 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ematologia con trapianto- AOU Policlinico Consorziale di Bari
  • Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
  • Università La Sapienza
  • Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
  • Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Everolimus

Arm Description

Everolimus mice-regimen

Outcomes

Primary Outcome Measures

Maximum-tolerated dose of everolimus
MTD of RAD given in combination with the MICE regimen

Secondary Outcome Measures

Safety
Complete remission rate
Complete remission rate (CR + CRi) following one or two induction courses.

Full Information

First Posted
June 29, 2010
Last Updated
October 24, 2022
Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto
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1. Study Identification

Unique Protocol Identification Number
NCT01154439
Brief Title
Everolimus MICE-regimen in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia
Acronym
AML1208
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 Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
October 2010 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
September 15, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gruppo Italiano Malattie EMatologiche dell'Adulto

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Everolimus
Arm Type
Experimental
Arm Description
Everolimus mice-regimen
Intervention Type
Drug
Intervention Name(s)
cytarabine
Other Intervention Name(s)
Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Intervention Description
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
Intervention Name(s)
etoposide
Other Intervention Name(s)
Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Intervention Description
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
Intervention Name(s)
everolimus
Other Intervention Name(s)
RAD001
Intervention Description
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
Intervention Name(s)
idarubicin
Other Intervention Name(s)
Mini-ICE regimen (idarubicin, cytarabine and etoposide).
Intervention Description
Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.
Intervention Type
Drug
Intervention Name(s)
mitoxantrone hydrochloride
Intervention Description
Remission induction therapy: by short i.v. infusion on days 1, 3 and 5
Primary Outcome Measure Information:
Title
Maximum-tolerated dose of everolimus
Description
MTD of RAD given in combination with the MICE regimen
Time Frame
At one year from study entry
Secondary Outcome Measure Information:
Title
Safety
Time Frame
At one year from study entry
Title
Complete remission rate
Description
Complete remission rate (CR + CRi) following one or two induction courses.
Time Frame
At one year from study entry

10. Eligibility

Sex
All
Minimum Age & Unit of Time
61 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sergio Amadori, MD
Organizational Affiliation
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ematologia con trapianto- AOU Policlinico Consorziale di Bari
City
Bari
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia
City
Napoli
Country
Italy
Facility Name
Università La Sapienza
City
Roma
ZIP/Postal Code
00100
Country
Italy
Facility Name
Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia
City
Roma
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
City
Rome
ZIP/Postal Code
00133
Country
Italy

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.gimema.it
Description
GIMEMA Foundation Website

Learn more about this trial

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

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