Study on All-Trans Retinoic Acid, Induction and Consolidation Therapy, and Pegfilgrastim After Consolidation Therapy in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This trial is a study on all-trans retinoic acid in combination with induction and consolidation therapy as well as pegfilgrastim after consolidation therapy in younger 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 1-7 Idarubicin 12 mg/m² i.v. days 1,3,5 Etoposide 100 mg/m² i.v. days 1-3 ± ATRA 45 mg/m² p.o. days 6-8 ATRA 15 mg/m² p.o. days 9-21 Second Induction Therapy: Cytarabine 100 mg/m² cont. i.v. days 1-7 Idarubicin 12 mg/m² i.v. days 1 and 3 Etoposide 100 mg/m² i.v. days 1-3 ± ATRA 45 mg/m² p.o. days 6-8 ATRA 15 mg/m² p.o. days 9-21 Consolidation Therapy: cohort 1 (<= ID 336) Cytarabine 3 g/m² 2x/die i.v. Tag 1,3,5 ± ATRA 15 mg/m² p.o. Tag 6-21 Pegfilgrastim 6 mg s.c day 10 cohort 2 (> ID 336) Cytarabine 3 g/m² 2x/die i.v. Tag 1,2,3 ± ATRA 15 mg/m² p.o. Tag 4-21 Pegfilgrastim 6 mg s.c day 8

Official Title
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Randomized Phase II/III-Study on All-Trans Retinoic Acid in Combination With Induction and Consolidation Therapy as Well as Pegfilgrastim After Consolidation Therapy in Younger 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: Etoposide
* Drug: All-trans retinoic acid
* Drug: Pegfilgrastim


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]) Ages 18-60 years Written informed consent of each patient at study entry. Molecular and cytogenetical diagnostics on initial bone marrow and peripheral blood specimen at the central reference laboratories Exclusion Criteria: Bleeding independent of the AML Acute promyelocytic leukemia Uncontrollable infection Participation in a concurrent clinical study Insufficiency of the kidneys (creatinine > 1.5x upper normal serum level), of the liver (bilirubin, AST or AP > 2x upper normal serum level), severe obstructive or restrictive ventilation disorder, heart failure New York Heart Association (NYHA) III/IV Severe neurological or psychiatric disorder interfering with ability to give an informed consent. No consent for registration, storage and processing of the individual disease-characteristics and course. Performance status WHO > 2 Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Cytarabine<br>* 100mg/m² kont. i.v. day 1-7 (induction therapy) 3g/m² 2x/die i.v. day 1,3,5 or day 1,2,3<br>Drug: Idarubicin<br>* 12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle)<br>Drug: Etoposide<br>* 100mg/m² i.v. day 1-3 (induction therapy)<br>Drug: Pegfilgrastim<br>* 6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2)<br>* Other names: Neulasta;|
| Experimental: 2<br> | Drug: Cytarabine<br>* 100mg/m² kont. i.v. day 1-7 (induction therapy) 3g/m² 2x/die i.v. day 1,3,5 or day 1,2,3<br>Drug: Idarubicin<br>* 12mg/m² i.v. day 1,3,5 (first induction cycle) 12mg/m² i.v. Tag 1,3 (second induction cycle)<br>Drug: Etoposide<br>* 100mg/m² i.v. day 1-3 (induction therapy)<br>Drug: All-trans retinoic acid<br>* 45mg/m² p.o. day 6-8 (induction therapy) 15mg/m² p.o. day 9-21 (induction therapy) 15mg/m² p.o. day 6-21 (consolidation therapy)<br>Drug: Pegfilgrastim<br>* 6mg s.c day 10 (cohort 1), 6mg s.c. day 8 (cohort 2)<br>* Other names: Neulasta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission (CR)-rate after induction therapy |  | after the second induction cycle | 
| Relapse-free survival, one year after consolidation therapy with high-dose cytarabine considering different temporal sequences (1-3-5 versus 1-2-3) of the consolidation therapy |  | One year after consolidation therapy | 
| 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 | 
| Cumulative incidence of relapse |  | two years | 
| Cumulative incidence of death |  | two years | 
| Overall survival |  | two years | 
| Hematological recovery as well as incidence and duration of infections during neutropenia after each consolidation cycle |  | during consolidation therapy | 
| Timely sequence of the pegfilgrastim-concentration in correlation to the absolute neutrophil counts after each consolidation cycle |  | during consolidation therapy | 
| Hematologic and non-hematologic toxicity after consolidation therapy with high-dose cytarabine considering the different consolidation schemes (day 1-3-5 versus day 1-2-3) |  | during consolidation therapy | 
| Days in hospital after each consolidation cycle |  | after consolidation therapy |