Ignite Creation Date:
2024-05-06 @ 1:18 PM
Last Modification Date:
2024-10-26 @ 1:12 PM
Study NCT ID:
NCT03989713
Status:
TERMINATED
Last Update Posted:
2022-09-15
First Post:
2019-04-12
Brief Title:
Quizartinib and High-dose Ara-C Plus Mitoxantrone in RelapsedRefractory AML With FLT3-ITD
Sponsor:
Prof Dr Richard F Schlenk
Organization:
University Hospital Heidelberg
Study Overview
Official Title:
Quizartinib and High-dose Ara-C Plus Mitoxantrone in RelapsedRefractory AML With FLT3-ITD
Status:
TERMINATED
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study turned out no longer feasible
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Q-HAM
Brief Summary:
In this multicenter upfront randomized phase II trial all patients receive quizartinib in combination with HAM high-dose cytarabine mitoxantrone during salvage therapy Efficacy is assessed by comparison to historical controls based on the matched threshold crossing approach During consolidation therapy chemotherapy as well as allo-HCT patients receive either prophylactic quizartinib therapy or MRD-triggered preemptive continuation therapy with quizartinib according to up-front randomization
Detailed Description:
Acute myeloid leukemia AML is a clonal malignant disorder which is characterized by the expansion of leukemic blasts in the bone marrow and the peripheral blood which goes along with a suppression of normal hematopoiesis including granulopoiesis erythropoiesis and thrombocytopoiesis The prognosis is largely determined by cytogenetic and molecular risk factors age performance status and antecedent myelodysplastic syndrome MDS With the exception of old and frail patients most AML patients are eligible for intensive chemotherapy which is given in curative intent consisting of induction and consolidation therapy However despite intensive therapy the long-term outcome of AML patients remains poor with less than 30 of patients achieving long lasting remission and even cure This poor outcome is largely due to refractoriness to induction chemotherapy as well as relapses during and after completion of intensive induction and consolidation therapy Regarding refractoriness about 20-30 of AML patients under the age of 60 years and about 50 of older patients fail to attain complete remission CR following cytarabine plus anthracycline based standard induction therapy In addition patients having achieved CR are at a high risk of relapse particularly within the first two years after completion of chemotherapy Allogeneic hematopoietic cell transplantation allo-HCT is currently the only treatment strategy to offer the prospect of cure in relapsedrefractory rr-AML but outcome after allo-HCT is largely determined by the remission state before allo-HCT With the aim to induce a CR before allo-HCT salvage chemotherapy regimens are administered in rr-AML Typically these salvage regimens are based on high dose cytarabine HiDAC which is frequently combined with either mitoxantrone HAM regimen or fludarabine plus idarubicin idaFLA regimen However there is still no commonly accepted standard salvage regimen and overall CR rates remain low with less than one third of the patients achieving a CR Apart from already known clinical unfavorable prognostic parameters in relapsed AML such as short first CR duration older age and previous allo-HCT FLT3-ITD has consistently been identified as an unfavorable molecular marker in both relapsed and refractory AML Recently midostaurin has been approved by the FDA and EMA for the treatment of newly diagnosed AML with activating FLT3 mutations But still roughly one quarter of patients who received midostaurin was refractory to induction therapy and relapse rate at 2 years excited 40 Thus new treatment options are urgently needed particularly in rr-AML with FLT3-ITD
The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3 has a high capacity for sustained FLT3 inhibition and an acceptable toxicity profile Furthermore single agent quizartinib doubled the response rate as compared to standard of care in a randomized study in rr-AML Although survival was also improved in this study the difference was only marginal
In this protocol we evaluate the efficacy of quizartinib in combination with HAM high-dose cytarabine mitoxantrone as compared to historical controls based on the matched threshold crossing approach followed by randomized prophylactic versus MRD-triggered continuation therapy with quizartinib including consolidation chemotherapy as well as allo-HCT and maintenance
The oral second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3 has a high capacity for sustained FLT3 inhibition and an acceptable toxicity profile Furthermore single agent quizartinib doubled the response rate as compared to standard of care in a randomized study in rr-AML Although survival was also improved in this study the difference was only marginal
In this protocol we evaluate the efficacy of quizartinib in combination with HAM high-dose cytarabine mitoxantrone as compared to historical controls based on the matched threshold crossing approach followed by randomized prophylactic versus MRD-triggered continuation therapy with quizartinib including consolidation chemotherapy as well as allo-HCT and maintenance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None