Consolidation therapy with high dose cytarabine in combination with pegfilgrastim: results concerning clinical and pharmacokinetical aspects of the AMLSG.

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Presentation transcript:

Consolidation therapy with high dose cytarabine in combination with pegfilgrastim: results concerning clinical and pharmacokinetical aspects of the AMLSG trial in comparison to the German AML-Intergroup and AMLHD98A trials

CBF-AML Standard Risk C ICE I R InductionConsolidation A-ICE I A-ICE II AMLSG 7-04 Phase II CC High Risk Salvage AMLSG RD Dose-modified Conditioning MRD MUD haplo A-C C CC RD Karyotype ICE I A-ICE I A-ICE II A-C CR MRD-allogene Tpl. Vaproic acid C ICE II

Consolidation Schedule Cytarabine ± ATRA day6 3 g/m 2 2x/die 15 mg/m 2 ± Valproic acid p.o. serum-level-adapted, aspired plasma level 100mg/l (60-150mg/l) 10 PEG-filgrastim 6mg

Current status: drug supply patients n=58 entered consolidation therapy n=42 PEG-filgrastim ordered correctly in the study office n=2 PEG-filgrastim not ordered in the study office n=2 Neupogen n=6 no G-CSF at all n=6 treated in the German AML Intergroup protocol

Available probes Consolidation In=58 No. patients n=6 consolidation IIn=22 No. patientsn=3 consolidation IIIn=22 No. patientsn=4  probesn=102 analyzedn=74 patientsn=5 Current status: pharmacokinetics

MedianRange Baseline-level0.55 ng/ml ng/ml Peak-level 24-48h220 ng/ml ng/ml Median terminal half-life5 days 3-7 days Current status: pharmacokinetics

Current status: pharmacokinetics study G-CSF serum level [ng/ml] WBC count [/nl] EC 90 EC 50 Cycle ICycle IICycle III

Current status: pharmacokinetics study G-CSF serum level [ng/ml] WBC count [/nl] EC 90 EC 50 ID 4 Cycle IID 11 Cycle IID 14 Cycle I

Comparison: AMLSG versus Intergroup versus AMLHD98A MedianRangefevern AMLSG days15-35 days15 (54%)28 -Standard20 days15-29 days11 -ATRA18 days15-26 days5 -VPA20.5 days16-30 days8 -ATRA-VPA22 days16-35 days4 Intergroup21.5 days19-33 days10 (77%)13 interventional GCSF n=1 AMLHD98A19 days15-29 days 434 (57%)532 HAM-regimen, interventional GCSF n=38 Leukopenia defined as difference between day 1 of treatment and first day with stable WBC counts >1x10 9 /l

Amendment No. I AMLSG Study Reduction of the idarubicin dosage in second induction therapy from 12mg/m² days 1, 3, 5 to days 1+3 Transition from i.v. to p.o. treatment with valproic acid irrespective from the achieved serum-level Abbreviation of consolidation therapy ARAC 3g/m² bid days 1, 3, 5 to days 1, 2, 3