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

Phase 1

Completed

• Conditions: Leukemia
• Interventions: Drug: cytarabine; Drug: etoposide; Drug: everolimus; Drug: idarubicin; Drug: mitoxantrone hydrochloride

• Registration Number: NCT01154439
• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

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.

Study Timeline

• Study First Submitted: 2010-06-29
• Study First Submitted QC: 2010-06-29
• Study First Posted: 2010-06-30
• Study Start: 2010-10
• Primary Completion: 2013-05
• Study Completion: 2015-09-15
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-24
• Last Update Posted: 2022-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Everolimus	cytarabine	Everolimus mice-regimen
Everolimus	etoposide	Everolimus mice-regimen
Everolimus	mitoxantrone hydrochloride	Everolimus mice-regimen
Everolimus	idarubicin	Everolimus mice-regimen
Everolimus	everolimus	Everolimus mice-regimen

Primary Outcome Measures

Name	Time	Method
Maximum-tolerated dose of everolimus	At one year from study entry	MTD of RAD given in combination with the MICE regimen

Secondary Outcome Measures

Name	Time	Method
Safety	At one year from study entry
Complete remission rate	At one year from study entry	Complete remission rate (CR + CRi) following one or two induction courses.

Trial Locations

Locations (5)

Università La Sapienza; 🇮🇹 Roma, Italy

Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia; 🇮🇹 Napoli, Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata; 🇮🇹 Rome, Italy

Ematologia con trapianto- AOU Policlinico Consorziale di Bari; 🇮🇹 Bari, Italy

Università degli Studi "Sapienza" - Dip Biotecnologie Cellulari ed Ematologia - Divisione di Ematologia; 🇮🇹 Roma, Italy