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CBF-AML Standard Risk

Consolidation therapy with high dose cytarabine in combination with pegfilgrastim: results concerning clinical and pharmacokinetical aspects of the AMLSG 07-04 trial in comparison to the German AML-Intergroup and AMLHD98A trials. AMLSG 7-04 Phase II. Induction. Consolidation. MRD-allogene Tpl.

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CBF-AML Standard Risk

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  1. Consolidation therapy with high dose cytarabine in combination with pegfilgrastim: results concerning clinical and pharmacokinetical aspects of the AMLSG 07-04 trial in comparison to the German AML-Intergroup and AMLHD98A trials

  2. AMLSG 7-04 Phase II Induction Consolidation MRD-allogene Tpl. C C C C ICE I ICE II A-C A-C A-C A-ICE II A-ICE I CR R CBF-AML Standard Risk C C C ICE I ICE II Vaproic acid Vaproic acid A-C A-C A-C A-ICE II A-ICE I Vaproic acid Vaproic acid RDKaryotype RD MRD MUD haplo Dose-modifiedConditioning SalvageAMLSG 05-04 High Risk

  3. Consolidation Schedule PEG-filgrastim 6mg Cytarabine 3 g/m2 2x/die 15 mg/m2 ± ATRA ± Valproic acid p.o. serum-level-adapted,aspired plasma level 100mg/l (60-150mg/l) 10 day 1 2 3 4 5 6 28

  4. 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

  5. Current status: pharmacokinetics Available probes Consolidation I n=58 No. patients n=6 consolidation II n=22 No. patients n=3 consolidation III n=22 No. patients n=4  probes n=102 analyzed n=74 patients n=5

  6. Current status: pharmacokinetics Median Range Baseline-level 0.55 ng/ml 0.38-0.72 ng/ml Peak-level 24-48h 220 ng/ml 61-501 ng/ml Median terminal half-life 5 days 3-7 days

  7. Current status: pharmacokinetics study G-CSF serum level [ng/ml] WBC count [/nl] EC90 EC50 Cycle I Cycle II Cycle III

  8. Current status: pharmacokinetics study G-CSF serum level [ng/ml] WBC count [/nl] EC90 EC50 ID 4 Cycle I ID 11 Cycle I ID 14 Cycle I

  9. Comparison: AMLSG 07-04 versus Intergroup versus AMLHD98A Median Range fever n AMLSG 07-04 20 days 15-35 days 15 (54%) 28 -Standard 20 days 15-29 days 11 -ATRA 18 days 15-26 days 5 -VPA 20.5 days 16-30 days 8 -ATRA-VPA 22 days 16-35 days 4 Intergroup 21.5 days 19-33 days 10 (77%) 13 interventional GCSF n=1 AMLHD98A 19 days 15-29 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 >1x109/l

  10. Amendment No. I AMLSG 07-04 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 therapyARAC 3g/m² bid days 1, 3, 5 to days 1, 2, 3

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