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LeukemiaPhase 1AML1208NCT01154439

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

A Phase 1 study testing cytarabine, etoposide and everolimus in people with Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 5 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 61 to 75 years
Conditions the study is for
Leukemia
What is being tested?
cytarabine, etoposide and everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
5 sitesItaly
Study dates
Oct 2010to 15 Sep 2015
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 61 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Italy5 sites
  • Ematologia con trapianto- AOU Policlinico Consorziale di Bari

    Bari

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

    Naples

  • Università La Sapienza

    Roma, 00100

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

    Roma

  • Azienda Ospedaliera Universitaria Policlinico Tor Vergata

    Rome, 00133

Other trials in Italy

About this study

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)

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.

Read the 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.

Conditions
Leukemia
Being tested
cytarabine, etoposide, everolimus, idarubicin, mitoxantrone hydrochloride
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)
Medical subject headings
Leukemia, Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cytarabineDrug

    Also called Mini-ICE regimen (idarubicin, cytarabine and etoposide).

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

  • etoposideDrug

    Also called Mini-ICE regimen (idarubicin, cytarabine and etoposide).

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

  • everolimusDrug

    Also called RAD001

    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.

  • idarubicinDrug

    Also called Mini-ICE regimen (idarubicin, cytarabine and etoposide).

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

  • mitoxantrone hydrochlorideDrug

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

Study groups in NCT01154439
Study groupRoleWhat they receive
EverolimusExperimentalEverolimus mice-regimen
Receives: Drug: cytarabine; Drug: etoposide; Drug: everolimus; Drug: idarubicin; Drug: mitoxantrone hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum-tolerated dose of everolimus

    MTD of RAD given in combination with the MICE regimen

    Measured: At one year from study entry

Secondary outcomes (2)
  1. Safety

    Measured: At one year from study entry

  2. Complete remission rate

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

    Measured: At one year from study entry

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jun 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionMay 2013
  4. Study completion15 Sep 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01154439
Sponsor's protocol ID
AML1208
Other IDs
GIMEMA-AML1208, 2008-007666-28, 2008
Acronym
AML1208
Status last verified
Oct 2022
First submitted
29 Jun 2010
Last updated
26 Oct 2022
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cytarabine, etoposide and everolimus in people with Leukemia, run by Gruppo Italiano Malattie EMatologiche dell'Adulto at 5 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum-tolerated dose of everolimus (time frame: At one year from study entry). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2022.

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