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Chemotherapy With or Without Gemtuzumab Ozogamicin in Treating Older Patients With Acute Myeloid Leukemia

Registration Number
NCT00052299
Lead Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. It is not yet known if combining combination chemotherapy with monoclonal antibody therapy will kill more cancer cells.

PURPOSE: Randomized phase III trial to determine the effectiveness of combination chemotherapy with or without gemtuzumab ozogamicin in treating patients who have acute myeloid leukemia.

Detailed Description

OBJECTIVES:

* Determine the antileukemic activity of standard induction chemotherapy with or without gemtuzumab ozogamicin in elderly patients with previously untreated acute myeloid leukemia.

* Determine the overall survival of patients treated with these regimens.

* Determine the rate of response, disease-free survival, event-free survival, incidence of relapse, and incidence of death of patients treated with these regimens.

* Determine the rate, type, and grade of toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to age (61-69 vs 70-75), CD33 positivity (less than 5% vs 5-19% vs 20-80% vs more than 80% vs unknown), initial WBC before hydroxyurea administration if needed (less than 30,000/mm\^3 vs at least 30,000/mm\^3), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I:

* Induction (phase I): Patients receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15.

* Induction (phase II/MICE regimen): Beginning between days 50 and 53, patients receive mitoxantrone IV over 30 minutes on days 1, 3, and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-7. Bone marrow evaluation is performed on day 29. Patients with partial remission (PR) receive a second course of MICE chemotherapy regimen. Patients with complete remission (CR) after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients with progressive disease go off therapy.

* Consolidation: Beginning within 4 weeks of documentation of CR, patients receive gemtuzumab ozogamicin IV over 2 hours on day 0; idarubicin IV on days 1, 3, and 5; etoposide IV over 1 hour on days 1-3; and cytarabine IV continuously on days 1-5. After at least day 30, patients receive a second consolidation course in the absence of disease progression or unacceptable toxicity.

* Arm II:

* Induction (MICE regimen): Patients receive mitoxantrone, etoposide, and cytarabine as in arm I induction. Bone marrow evaluation is performed on day 29. Patients with PR receive a second course of MICE chemotherapy regimen. Patients with CR after 1 or 2 courses of MICE regimen proceed to consolidation therapy. Patients with progressive disease go off therapy.

* Consolidation: Patients receive idarubicin, etoposide, and cytarabine as in arm I consolidation.

Patients are followed monthly for 1 year, every 3 months for 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 450 patients (225 per treatment arm) will be accrued for this study within 3.75 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
472
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ARM Amitoxantrone hydrochlorideGO + MICE for remission induction followed by GO + mini-ICE for consolidation
ARM Bmitoxantrone hydrochlorideMICE for remission induction followed by mini-ICE for consolidation
ARM AcytarabineGO + MICE for remission induction followed by GO + mini-ICE for consolidation
ARM AetoposideGO + MICE for remission induction followed by GO + mini-ICE for consolidation
ARM Agemtuzumab ozogamicinGO + MICE for remission induction followed by GO + mini-ICE for consolidation
ARM AidarubicinGO + MICE for remission induction followed by GO + mini-ICE for consolidation
ARM BcytarabineMICE for remission induction followed by mini-ICE for consolidation
ARM BidarubicinMICE for remission induction followed by mini-ICE for consolidation
ARM BetoposideMICE for remission induction followed by mini-ICE for consolidation
Primary Outcome Measures
NameTimeMethod
Overall survival
Secondary Outcome Measures
NameTimeMethod
Response (complete remission [CR] or complete remission with incomplete recovery of platelet count [CRp]) rate after induction
Disease-free survival after CR/CRp
Event-free survival
Toxicity (highest grade) assessed by International Working Group CTC v2.0
Incidence of relapse after CR/CRp
Incidence of death without relapse after CR/CRp

Trial Locations

Locations (55)

A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung

🇦🇹

Linz, Austria

Allgemeines Krankenhaus - Universitatskliniken

🇦🇹

Vienna, Austria

AZ Sint-Jan

🇧🇪

Brugge, Belgium

Institut Jules Bordet

🇧🇪

Brussels, Belgium

Hopital Universitaire Erasme

🇧🇪

Brussels, Belgium

Centre Hospitalier Universitaire Brugmann

🇧🇪

Brussels, Belgium

Universitair Ziekenhuis Antwerpen

🇧🇪

Edegem, Belgium

Hopital de Jolimont

🇧🇪

Haine Saint Paul, Belgium

CHU Liege - Domaine Universitaire du Sart Tilman

🇧🇪

Liege, Belgium

Centre Hospitalier Peltzer-La Tourelle

🇧🇪

Verviers, Belgium

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A. oe. Krankenhaus der Barmherzigen Schwestern Kinderabteilung
🇦🇹Linz, Austria

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