BI 811283 in Combination With Cytarabine in Previously Untreated AML Ineligible for Intensive Treatment
- Conditions
- Leukemia, Myeloid, Acute
- Interventions
- Registration Number
- NCT00632749
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Investigation of maximum tolerated dose, safety, efficacy and pharmcokinetics of BI 811283 in combination with cytarabine (LD-Ara-C) in previously untreated acute myeloid leukaemia (AML) patients
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 68
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Schedule A BI 811283 (d 1 and 15) BI 811283 on days 1 and 15 in combination with Cytarabine 20 mg twice daily on Days 1-10 Schedule B BI 811283 (d1) BI 811283 on Day 1 in combination with Cytarabine 20 mg twice daily on Days 1-10 Schedule A Cytarabine BI 811283 on days 1 and 15 in combination with Cytarabine 20 mg twice daily on Days 1-10 Schedule B Cytarabine BI 811283 on Day 1 in combination with Cytarabine 20 mg twice daily on Days 1-10
- Primary Outcome Measures
Name Time Method The Maximum Tolerated Dose (MTD) of 2 Schedules of BI 811283 in Combination With Cytarabine. up to 28 days of treatment The MTD was defined as the highest dose at which 6 patients were treated and less than 2 patients who experienced a dose limiting toxicities (DLT) within the first cycle of treatment.The MTD was defined based on safety data from the first cycle only.
It was determined using a standard "3 + 3 design with de-escalation".
- Secondary Outcome Measures
Name Time Method Response (Complete Remission [CR], Complete Remission With Incomplete Blood Count Recovery [CRi]) Data collected up to cut-off date 20Oct2011, Up to 1239 days Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria:
The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment.
* Complete remission (CR): morphologically leukaemia free state (i.e. bone marrow with \< 5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥ 1,000/μL and platelets \> 100,000/μL.
* Complete remission with incomplete blood count recovery ("incomplete" CR, CRi).All of the above criteria for CR had to be met, except that neutrophils \< 1,000/μL or platelets \< 100,000/μL in the blood.Incidence and Intensity of AEs Graded According to CTCAE (Version 3.0) Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days The severity and timing of AEs indicates how well the treatment regimen was tolerated.
Toxicities were evaluated using the common terminology criteria for adverse events (CTCAE) grading scheme.Incidence of Dose Limiting Toxicity (DLT) up to 28 days of treatment Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD)
Partial Remission Data collected up to cut-off date 20 Oct 2011, Up to 1239 days Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria; The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment.
Partial remission (PR). All of the criteria for CR had to be met, except that the bone marrow had to contain ≥ 5% but less than 25% blasts (or ≤ 50% of initial blast count), or \< 5% blasts in the presence of Auer rods or abnormal morphology.Event Free Survival (EFS) Data collected up to cut-off date 20 Oct 2011, Up to 1239 days EFS was defined as the duration of time from randomisation to time of treatment failure (i.e. PD), relapse from CR, or death from any cause, whichever came first.
Relapse Free Survival Data collected up to cut-off date 20 Oct 2011, Up to 1239 days Relapse-free survival was defined only for patients who achieved CR/CRi and was measured from the date of attaining CR/CRi until the date of recurrence or death from any cause, whichever occurred first.
Number of patients having relapse free survival are presented.Remission Duration Data collected up to cut-off date 20 Oct 2011, Up to 1239 days Remission duration analysis was defined only for patients who achieved CR, and was measured from the date of attaining CR until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of the cause.
Overall Survival (OS) Data collected up to cut-off date 20 Oct 2011, Up to 1239 days OS was defined for all patients that entered the trial, and measured from the date of randomization until death from any cause.
Cmax (Maximum Measured Concentration of BI 811283 in Plasma) -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 Cmax (maximum measured concentration of BI 811283 in plasma) during Cycle 1
AUC(0-inf) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) during Cycle 1
AUC0-tz (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) during Cycle 1
Cmax,ss (Maximum Measured Concentration of BI 811283 in Plasma at Steady State) -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 Cmax (maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1
AUC (0-inf, ss)(Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 Extrapolated to Infinity) at Steady State -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state during Cycle 1
AUC (0-tz,ss) (Area Under the Concentration-time Curve of BI 811283 in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) at Steady State -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state during Cycle 1
Tmax (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma) -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 tmax (time from dosing to maximum measured concentration of BI 811283 in plasma) during Cycle 1
Tmax,ss (Time From Dosing to Maximum Measured Concentration of BI 811283 in Plasma at Steady State) -0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283 tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1
Cmax (Maximum Measured Concentration of Cytarabine in Plasma) -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine Cmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
Tmax (Time From Dosing to Maximum Measured Concentration of Cytarabine in Plasma) -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine Tmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
AUC (0-inf) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 Extrapolated to Infinity) -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine AUC (0-inf) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
AUC (0-tz) (Area Under the Concentration-time Curve of Cytarabine in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) -0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine AUC (0-tz) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283
Pharmacodynamic Monitoring On Day 5, i.e. 72 hours after the end of the first BI 811283 infusion, and on Day 28 in the first cycle only Pharmacodynamic monitoring: drug effect on leukaemia cells (e.g. polyploidy, histone H3 phosphorylation, morphologic changes).
An evaluation of this secondary endpoint is not possible due to missing samples / samples of poor quality of the provided material.Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone -0.05, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours The study protocol originally included a phase II part with a treatment arm in which Cytarabine was given alone, however the sponsor discontinued the clinical development of BI 811283, therefore the protocol was amended and the reference therapy arm was removed from the study protocol" -\> (Protocol Amendment 5, version 19 -May-2010, approved 28-Jun-2010).
Since there was never a treatment arm in which Cytarabine was given alone; hence pharmacokinetics are not calculated.
Trial Locations
- Locations (7)
1247.3.49004 Boehringer Ingelheim Investigational Site
🇩🇪Freiburg, Germany
1247.3.49007 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
1247.3.49005 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt/Main, Germany
1247.3.49006 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
1247.3.49002 Boehringer Ingelheim Investigational Site
🇩🇪Münster, Germany
1247.3.49003 Boehringer Ingelheim Investigational Site
🇩🇪Heidelberg, Germany
1247.3.49001 Boehringer Ingelheim Investigational Site
🇩🇪Ulm, Germany