Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02013648|
Recruitment Status : Recruiting
First Posted : December 17, 2013
Last Update Posted : December 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (AML)||Drug: Dasatinib Drug: Cytarabine Drug: Daunorubicin||Phase 3|
This is a randomized phase III open-label, multicenter trial evaluating standard induction therapy (daunorubicin [DNR] and cytarabine [Ara-C]) and consolidation therapy (high-dose cytarabine [HDAC]) with or without dasatinib in adult patients with newly diagnosed CBF-AML; in the investigational arm, consolidation therapy is followed by a one-year maintenance therapy with dasatinib. Patients with molecular disease persistence or molecular relapse as assessed by quantitative RQ-PCR for the CBF fusion transcripts will be eligible for hematopoietic stem cell transplantation before overt hematologic relapse occurs. Primary endpoint is event-free survival.
AML patients will be assessed for the CBF fusion genes in one of two AMLSG central laboratories within 48 hours of diagnosis, and only patients with CBF-AML will be enrolled.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||277 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomized Phase III Study of Intensive Chemotherapy With or Without Dasatinib (Sprycel™) in Adult Patients With Newly Diagnosed Core-Binding Factor Acute Myeloid Leukemia (CBF-AML)|
|Study Start Date :||July 2014|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||May 2023|
Active Comparator: Standard arm
Patients will receive induction therapy (one or two cycles) with daunorubicin 60 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by continuous IV infusion on days 1-7. No dose reduction is planned in elderly (>60 years) patients.
Optional second induction cycle:
Patients achieving PR only at the end of cycle 1 will receive a second induction cycle with daunorubicin 50 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by cont. IV infusion daily on days 1-5.
Patients will receive 4 cycles of consolidation therapy. Consolidation therapy consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, days 1-3 administered intravenously over three hours.
There is no maintenance therapy in the standard arm. Patients will be closely followed, in particular for molecular disease persistence or molecular relapse.
Other Name: ARA-cell
Other Name: Daunoblastin
Experimental: Investigational arm
Patients will receive induction therapy (one or two cycles) with daunorubicin 60 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by continuous IV infusion on days 1-7. Patients will receive dasatinib 100 mg once daily (QD) on days 8-21.
Opt. 2nd induction cycle:
Patients achieving PR only at the end of cycle 1 will receive a 2nd induction cycle with daunorubicin 50 mg/m2/day administered on days 1-3 and cytarabine 200 mg/m2/day administered by cont. IV infusion on days 1-5. Patients will receive dasatinib 100 mg QD on days 6-21.
Patients will receive 4 consolidation cycles. Treatment consists of high-dose cytarabine 3 g/m2 (>60 years: 1 g/m2) q12h, days 1-3 administered IV over 3 hours. Patients will receive dasatinib 100 mg QD on days 4-21.
Patients completing consolidation therapy will continue to receive single agent dasatinib 100 mg QD for one year (or until relapse).
Other Name: Sprycel
Other Name: ARA-cell
Other Name: Daunoblastin
- Event-free Survival [ Time Frame: 4 years ]To assess event-free survival (EFS) after intensive induction (daunorubicin and cytarabine) and consolidation (high-dose cytarabine) chemotherapy with or without dasatinib in patients with CBF-AML
- Cumulative incidence of relapse (CIR) [ Time Frame: 4 years ]
- Cumulative incidence of death (CID) [ Time Frame: 4 years ]
- overall survival [ Time Frame: 4 years ]
- relapse-free survival [ Time Frame: 4 years ]
- PIA analysis [ Time Frame: 4 years ]Pharmacodynamic inhibition of KIT as assessed by the KIT plasma inhibitory assay (PIA)
- toxicity [ Time Frame: 7 months (standard arm) / 19 months (investigational arm) ]Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03), timing and relatedness of non-hematologic toxicity observed during different treatment cycles.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02013648
|Contact: Hartmut Doehner, Prof. Dr.||0049-731-500- ext firstname.lastname@example.org|
|Contact: Peter Paschka, Dr.||0049-731-500 ext email@example.com|
Show 53 Study Locations
|Principal Investigator:||Hartmut Doehner, Prof. Dr.||University of Ulm|