Protocol in Acute Myeloid Leukemia With FLT3-ITD
This is a phase II, single-arm, open-label, multi-center study in adult patients with Acute Myeloid Leukemia (AML) and FLT3-ITD as defined in inclusion/exclusion criteria.
The primary efficacy object is to evaluate the impact of midostaurin given in combination with intensive induction, consolidation including allogeneic hematopoietic stem cell transplantation and single agent maintenance therapy on event-free survival (EFS) in adult patients with AML exhibiting a FLT3-ITD.
Sample size: 440 patients
The treatment duration of an individual patient is between 18 and 24 months. Duration of the study for an individual patient including treatment (induction, consolidation [chemotherapy or allogeneic SCT], maintenance and follow-up period: Maximum 7.5 years
Acute Myeloid Leukemia
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase-II Study Evaluating Midostaurin in Induction, Consolidation and Maintenance Therapy Also After Allogeneic Blood Stem Cell Transplantation in Patients With Newly Diagnosed Acute Myeloid Leukemia Exhibiting a FLT3 Internal Tandem Duplication|
- Event-free Survival [ Time Frame: 7.5 years ]To perform two predefined subgroup analyses in the age-groups 18-60 years and 61-70 years evaluating the impact of midostaurin given in combination with intensive induction, consolidation including allogeneic hematopoietic stem cell transplantation and single agent maintenance therapy on event-free survival (EFS) in adult patients with AML exhibiting a FLT3-ITD.
- Rate of complete remission (CR) [ Time Frame: Two months ]
- Relapse-free survival [ Time Frame: 7.5 years ]
- overall survival [ Time Frame: 7.5 years ]
- Cumulative incidence of relapse [ Time Frame: 7.5 years ]
- cumulative incidence of death in CR [ Time Frame: 7.5 years ]
- Target (FLT3) inhibition by measuring the FLT3 plasma inhibitory activity [ Time Frame: 7.5 years ]Evaluation of target (FLT3) inhibition by continuous dosing of midostaurin
- Quality of life [ Time Frame: 5 years ]Quality of life assessed by the EORTC Quality of Life Core Questionnaire (QLQ-C30), supplemented by information on self-assessed concomitant diseases, late treatment effects, and demographics initially, in first CR, after one year,3 and 5 years after initial diagnosis.
- Rate of early deaths and hypoplastic deaths (ED/HD) [ Time Frame: two months ]
- Death in CR [ Time Frame: 7.5 years ]
- Toxicities [ Time Frame: between 18 and 24 months ]Type, frequency, severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 3.0), timing and relatedness of hematological and non-hematological toxicities observed during the different treatment cycles
- Impact of allogeneic HSCT [ Time Frame: 7.5 years ]Assessment of the relative impact of allogeneic HSCT analyzed as time-dependent variable on survival endpoints.
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||December 2019 (Final data collection date for primary outcome measure)|
Induction therapy: 50 mg, oral, twice daily, starting on day 8, thereafter continuous dosing until 48h before start of subsequent chemotherapy cycle.
Consolidation therapy: 50 mg, oral twice daily, starting on day 6, thereafter continuous dosing until 48h before start of conditioning therapy for allogeneic HSCT or 48h before start of subsequent consolidation chemotherapy.
50 mg oral twice daily over one year.
Other Name: PKC412Drug: Cytarabine
200 mg/m2/day by continuous i.v. infusion on days 1-7 (total dose 1400 mg/m²)
Younger adult patients (18 to 65 yrs): 3 g/m2 by i.v infusion over 3 hours every 12 hours on days 1, 3, and 5 (total dose 18 g/m2).
Older patients (>65 yrs): 1 g/m2 by i.v. infusion over 3 hours every 12 hours on days 1, 3, and 5 (total dose 6 g/m2).
60 mg/m², by 1-hour i.v. infusion, day 1-3 (total dose 180 mg/m²)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01477606
|Contact: Peter Paschka, MDfirstname.lastname@example.org|
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|Principal Investigator:||Richard F Schlenk, MD||University Hospital of Ulm|