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

Leukemia Clinical Trial

— 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01154439
• Other study ID #: AML1208
• Secondary ID: GIMEMA-AML120820
• Status: Completed
• Phase: Phase 1
• Start date: October 2010
• Est. completion date: September 15, 2015

Study information

• Verified date: October 2022
• Source: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 15, 2015
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 61 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• cytarabine
Remission induction therapy: by short i.v. infusion on days 1 and 7. Consolidation therapy: by continuous infusion on days 1-5.
• etoposide
Remission induction therapy: by short i.v. infusion, on days 1-7. Consolidation therapy: by short i.v. infusion, on days 1-5.
• 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.
• idarubicin
Consolidation therapy: by short infusion i.c. on days 1, 3 and 5.
• mitoxantrone hydrochloride
Remission induction therapy: by short i.v. infusion on days 1, 3 and 5

Locations

Country	Name	City	State
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	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Gruppo Italiano Malattie EMatologiche dell'Adulto

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum-tolerated dose of everolimus	MTD of RAD given in combination with the MICE regimen	At one year from study entry
Secondary	Safety		At one year from study entry
Secondary	Complete remission rate	Complete remission rate (CR + CRi) following one or two induction courses.	At one year from study entry

External Links

•   GIMEMA Foundation Website