All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is a study looking at all-trans retinoic acid in combination with standard induction and consolidation therapy in older patients with newly diagnosed acute myeloid leukemia (AML).

Detailed Description
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First Induction Therapy: Cytarabine 100 mg/m² cont. i.v. days 1-5 Idarubicin 12 mg/m² i.v. days 1, 3 ATRA 45 mg/m² p.o. days 4-6, ATRA 15 mg/m² p.o. days 7-28 Second Induction Therapy: Cytarabine 100 mg/m² cont. i.v. days 1-5 Idarubicin 12 mg/m² i.v. days 1, 3 ATRA 45 mg/m² p.o. days 4-6, ATRA 15 mg/m² p.o. days 7-28 First Consolidation Therapy: Cytarabine 1000 mg/m² bid i.v. days 1-3 Mitoxantrone 10 mg/m² i.v. days 2, 3 ATRA 15 mg/m² p.o. days 4-28 Second Consolidation Therapy Etoposide 100 mg/m² i.v. days 1-5 Idarubicin 12 mg/m² i.v. days 1,3 ATRA 15 mg/m² p.o. days 4-28

Official Title
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Phase III - Study on All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Cytarabine
* Drug: Idarubicin
* Drug: All-trans retinoic acid
* Drug: Mitoxantrone
* Drug: Etoposid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed AML defined according to the World Health Organization (WHO) classification (excluding acute promyelocytic leukemia [APL]) Aged > 60 years All patients have to be informed about the character of the study. Written informed consent of each patient at study entry. Molecular and cytogenetical analyses on initial bone marrow and peripheral blood specimen have to be performed at the central reference laboratories. Exclusion Criteria: Bleeding independent of the AML Acute promyelocytic leukemia Uncontrolled infection Participation in a concurrent clinical study Insufficiency of the kidneys (creatinine > 1.5 x upper normal serum level), of the liver (bilirubin, AST or AP > 2 x upper normal serum level), severe obstruction or restrictive ventilation disorder, heart failure New York Heart Association [NYHA] III/IV Severe neurological or psychiatric disorder interfering with ability of giving informed consent No consent for the registration, storage and processing of data concerning the characteristics of the AML and the individual course Performance status WHO > 2

Ages Eligible for Study
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Minimum Age: 61 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cytarabine|100mg/m² kont. i.v. day 1-5 (induction therapy); 1000 mg/m² 2x/die i.v. day 1-3 (first consolidation cycle)|
|Drug: Idarubicin|12mg/m² i.v. day 1+3 (induction therapy); 12mg/m² i.v. Tag 1+3 (second consolidation cycle)|
|Drug: All-trans retinoic acid|45mg/m² p.o. day 4-6, 15mg/m² p.o. day 7-28 (induction therapy); 15mg/m² p.o. day 4-28 (consolidation therapy)|
|Drug: Mitoxantrone|10mg/m² i.v. day 2-3 (first consolidation cycle)|
|Drug: Etoposid|100mg/m² i.v. Tag 1-5 (second consolidation cycle)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event-free survival |  | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| kind, incidence, severity, temporal sequence and correlation of side effects of the study drugs |  | during therapy | 
| complete remission (CR) rate after induction therapy |  | after second induction cycle | 
| cumulative incidence of relapse |  | two years | 
| cumulative incidence of death |  | two years | 
| overall survival |  | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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age > 60 years