Leukemia, Myeloid, Acute
Conditions
Brief summary
Patients with acute myeloid leukemia who experience a relapse after at least one prior regimen may be enrolled in this trial. In addition, acute myeloid leukemia patients who are in complete remission with high risk to relapse may be eligible for this trial. The trial will examine whether monotherapy with BI 836858 is safe and tolerable at escalating dose levels.
Interventions
DRUGBI 836858
Monotherapy with BI 836858 administered as intravenous infusion
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of relapsed or refractory AML with at least one prior treatment for acute myeloid leukemia and patients with diagnosis of acute myeloid leukemia in complete remission with high risk to relapse. 2. Expression of CD33 on more than 30% of bone marrow blasts at screening for patients with refractory or relapsed acute myeloid leukemia is required. CD33 positive expression of bone marrow blasts at the time of initial acute myeloid leukemia diagnosis is sufficient for those patients in complete remission with high risk to relapse. 3. Eastern Cooperative Oncology Group Performance Status 0, 1 or 2 4. Age 18 years or older 5. Written informed consent which is consistent with International Conference on Harmonization, Good Clinical Practice (ICH-GCP) guidelines and local legislation.
Exclusion criteria
1. Patients with acute promyelocytic leukemia according to WHO definition. 2. Patients with refractory or relapsed acute myeloid leukemia \> 5.000 blasts in the peripheral blood. 3. Anti-leukemia therapy within two weeks before first treatment with BI 836858, 4 weeks for biologics. Parallel treatment with Hydroxyurea ia allowed with refractory or relapsed acute myeloid leukemia patients. 4. Allogeneic stem cell transplantation within the last 28 days before first treatment with graft versus host disease requiring more than 20 mg of steroids per day. Steroid dosage must be stable within two weeks prior to start of treatment. 5. Patients who are candidates for allogeneic stem cell transplantation (for patients with refractory or relapsed acute myeloid leukemia). 6. Second malignancy currently requiring active therapy. 7. Symptomatic central nervous system involvement 8. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than 2.5 times the upper limit of normal (ULN), or AST or ALT greater than 5 times the ULN for those with Gilbert syndrome. 9. Prothrombin time (PT) \>1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin) 10. Bilirubin greater than 1.5 mg/dl (\>26 µmol/L) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert syndrome, or hemolysis. 11. Serum creatinine greater than 2.0 mg/dl 12. Known human immunodeficiency virus (HIV) infection or active hepatitis B virus or hepatitis C virus infection. 13. Concomitant intercurrent illness, or any condition which in the opinion of the Investigator, would compromise safe participation in the study, e.g. active severe infection, unstable angina pectoris, new onset of exacerbation of a cardiac arrhythmia 14. Psychiatric illness or social situation that would limit compliance with trial requirements 15. Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug 16. Female patients of childbearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial and for 6 months after the last administration of BI 836858 17. Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second effective method of contraception during the trial and for 6 months after the last administration of BI 836858 18. Pregnant or nursing female patients 19. Treatment with another investigational agent under the following conditions: 1. Within two weeks (4 weeks for biologics or 5 half-lives, whichever is longer) of first administration of BI 836858; or 2. Patient has persistent toxicities from prior anti-leukemic therapies which are determined to be relevant by the Investigator. 3. Concomitant treatment with another investigational agent while participating in this trial. 20. Prior treatment with a CD33 antibody 21. Patient unable or unwilling to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the Maximum Tolerated Dose (MTD) of BI 836858 | From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days. | This trial was discontinued prior to reaching the primary endpoint of determining MTD. |
| Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation | From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days. | Dose limiting toxicity was defined as any non-disease-related, non-hematological Adverse Events (AE) of Common Terminology Criteria for AE (CTCAE) grade 3 or higher. Number of patients with DLT during the MTD evaluation period for evaluation for patients with refractory or relapsed acute myeloid leukemia, the first 2 cycles (i.e. patient received at least 4 administrations of BI 836858 and reached end of Cycle 2) and for AML patients in CR with high risk to relapse, the first 2 cycles (i.e. patient has received at least 2 administrations of BI 836858 and reached end of Cycle 2). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Treatment Failure for Patients With Refractory or Relapsed Acute Myeloid Leukemia | From first administration of study drug until progressive disease, relapse, death or start of next anti-AML therapy, up to 167 days. | Time to treatment was defined as the time from first treatment with BI 836858 until disease progression, relapse or death or start of next AML therapy. |
| Progression Free Survival for AML Patients in CR With High Risk to Relapse | From first treatment with study drug until disease progression, relapse or death for AML patients in CR with high risk to relapse, up to 409 days. | Progression-free survival was defined as the time from first treatment with BI 836858 until disease progression, relapse or death for AML patients in CR with high risk to relapse. |
| Time to Treatment Failure for AML Patients in CR With High Risk to Relapse | From first treatment with study drug until disease progression, relapse, death or start of next AML therapy for AML patients in CR with high risk to relapse, up to 409 days. | Time to treatment was defined as the time from first treatment with BI 836858 until disease progression, relapse or death or start of next AML therapy. |
| Maximum Measured Plasma Concentration (Cmax) | At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after BI 836858 infusion. | Maximum measured plasma concentration (Cmax) after the first infusion is presented. |
| Time From Dosing to the Maximum Plasma Concentration (Tmax) | At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after BI 836858 infusion. | Time from dosing to the maximum plasma concentration (tmax) after the first infusion is presented. |
| Area Under the Plasma Concentration-time Curve Over the Time Interval of One Week (AUC0-168) | At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after BI 836858 infusion. | Area under the plasma concentration-time curve over the time interval of one week (AUC0-168) after the first infusion is presented. |
| Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | At approximately 5 minutes (min) before start of first (Day 1) and second (Day 8) BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after first and second BI 836858 infusion. | Area under the plasma concentration-time curve over the time interval of one treatment cycle (AUC0-tz) is presented. One treatment cycle included a first and a second infusion. |
| Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | From first administration of study drug until the earliest of progressive disease (PD), death or last adequate disease assessment before new anti-cancer therapy, up to 299 days. | BOR for patients with refractory/relapsed acute myeloid leukemia defined as: -CR:Morphologically leukemia free state/absolute neutrophil count≥1000/microliter(μL)and platelets≥100,000/μL. No transfusion for 1week prior to assessment -CRi:Met criteria for CR, except absolute neutrophils\<1000/μl/platelets\<100,000/μl -PR:Met criteria for CR, except leukemic blasts in bone marrow may range from 5 to 25% as long as count has decreased by at least 50% from pre-study treatment, or\<5% blasts in presence of Auer rods or abnormal morphology -TF:Patient survives≥7 days following completion of initial 2 treatment cycles with persistent leukemia in the last peripheral blood smear or bone marrow or with persistent extramedullary disease - PD:Patient survives\>7 days following completion of initial 2 treatment cycles with increase of blast population in bone marrow or peripheral blood by\>50% or aggravation or new development of extramedullary disease or further deterioration or death due to leukemia |
| Terminal Half-life (t1/2) | At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion. | Terminal half-life (t1/2) is presented. |
| Mean Residence Time After Intravenous Infusion (MRT) | At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion. | Mean residence time after intravenous infusion (MRT) is presented. |
| Total Plasma Clearance (CL) | At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion. | Total plasma clearance (CL) is presented. |
| Apparent Volume of Distribution During the Terminal Phase (Vz) | At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion. | Apparent volume of distribution during the terminal phase (Vz) is presented. |
| Volume of Distribution After Intravenous Infusion at Steady State (Vss) | At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion. | Volume of distribution after intravenous infusion at steady state (Vss) is presented. |
| Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | At approximately 5 minutes (min) before start of first (Day 1) and second (Day 8) BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after first and second BI 836858 infusion. | Area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable data point (AUC0-tz) is presented. |
| Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-infinity) | At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion. | Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-infinity) is presented. |
| Progression Free Survival for Patients With Refractory or Relapsed Acute Myeloid Leukemia | From first administration of study drug until progressed according to disease assessment, relapse, or death without progression, up to 167 days. | Progression-free survival was defined as the time from first treatment with BI 836858 until disease progression, relapse or death. |
Countries
United States
Participant flow
Recruitment details
Phase1, open-label, non-randomized, dose-escalation, 3+3 design study followed by expansion cohort with two separate patient populations:1) patients diagnosed with relapsed or refractory acute myeloid leukemia (AML) who have failed at least one prior line of therapy(2) patients with AML who are in complete remission (CR) with high risk to relapse.
Pre-assignment details
This study initially enrolled patients diagnosed with refractory or relapsed AML who had failed at least 1 prior line of therapy and was later amended to include patients with AML who were in CR with a high risk to relapse.
Participants by arm
| Arm | Count |
|---|---|
| BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) Patients with relapsed\\refractory AML were administered BI 836858 10 mg solution for infusion intravenously on day 1 and day 8 of the 14-day cycles (1 cycle with 2 administrations). | 12 |
| BI 836858 20 mg (Patients With Relapsed\Refractory AML) Patients with relapsed\\refractory AML were administered BI 836858 20 mg solution for infusion intravenously on day 1 and day 8 of the 14-day cycles (1 cycle with 2 administrations). | 8 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) Patients with relapsed\\refractory AML were administered BI 836858 40 mg solution for infusion intravenously on day 1 and day 8 of the 14-day cycles (1 cycle with 2 administrations). | 7 |
| BI 836858 40 mg (Patients With AML in CR) Patients with AML in complete remission (CR) with high risk to relapse were administered BI 836858 40 mg solution for infusion intravenously on Day 1 of Cycles 1, 2 and 3. From the 4th administration onwards, patients received monthly (every second cycle) infusions (i.e. 4th infusion on Cycle 5 Day 1, 5th infusion on Cycle 7 Day 1, etc.) for overall up to 12 months of treatment unless the patient relapsed or infusions were not tolerated. | 3 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse event (other than DLT) | 3 | 1 | 1 | 1 |
| Overall Study | Lack of Efficacy | 1 | 1 | 3 | 0 |
| Overall Study | PD based on IWG criteria or clinical PD | 8 | 5 | 2 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Sponsor is ending trial | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | BI836858 10milligram(mg)(Patients With Relapsed\refractoryAML) | BI 836858 20 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With Relapsed\Refractory AML) | BI 836858 40 mg (Patients With AML in CR) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.0 Years STANDARD_DEVIATION 12.4 | 60.8 Years STANDARD_DEVIATION 7.6 | 72.3 Years STANDARD_DEVIATION 6.7 | 49.0 Years STANDARD_DEVIATION 17.5 | 62.4 Years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 5 Participants | 7 Participants | 3 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 3 Participants | 0 Participants | 0 Participants | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 6 Participants | 6 Participants | 3 Participants | 27 Participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 4 Participants | 1 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 3 Participants | 2 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 12 | 4 / 8 | 2 / 7 | 0 / 3 |
| other Total, other adverse events | 12 / 12 | 8 / 8 | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 9 / 12 | 8 / 8 | 6 / 7 | 1 / 3 |
Outcome results
Primary
Determination of the Maximum Tolerated Dose (MTD) of BI 836858
This trial was discontinued prior to reaching the primary endpoint of determining MTD.
Time frame: From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.
Population: MTD evaluable set (non-replaced patients) defined as patients who completed the first two treatment cycles.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Determination of the Maximum Tolerated Dose (MTD) of BI 836858 | NA Milligram (mg) |
| BI 836858 40 mg (Patients With AML in CR) | Determination of the Maximum Tolerated Dose (MTD) of BI 836858 | NA Milligram (mg) |
Primary
Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation
Dose limiting toxicity was defined as any non-disease-related, non-hematological Adverse Events (AE) of Common Terminology Criteria for AE (CTCAE) grade 3 or higher. Number of patients with DLT during the MTD evaluation period for evaluation for patients with refractory or relapsed acute myeloid leukemia, the first 2 cycles (i.e. patient received at least 4 administrations of BI 836858 and reached end of Cycle 2) and for AML patients in CR with high risk to relapse, the first 2 cycles (i.e. patient has received at least 2 administrations of BI 836858 and reached end of Cycle 2).
Time frame: From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.
Population: MTD evaluable set (non-replaced patients) defined as patients who completed the first two treatment cycles.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation | 2 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation | 0 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation | 0 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Number of Patients With Dose Limiting Toxicity (DLT) During MTD Evaluation | 0 Participants |
Secondary
Apparent Volume of Distribution During the Terminal Phase (Vz)
Apparent volume of distribution during the terminal phase (Vz) is presented.
Time frame: At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Apparent Volume of Distribution During the Terminal Phase (Vz) | 6.99 Litre (l) | Geometric Coefficient of Variation 51.9 |
| BI 836858 40 mg (Patients With AML in CR) | Apparent Volume of Distribution During the Terminal Phase (Vz) | 6.29 Litre (l) | Geometric Coefficient of Variation 30.8 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Apparent Volume of Distribution During the Terminal Phase (Vz) | 6.72 Litre (l) | Geometric Coefficient of Variation 63.9 |
| BI 836858 40 mg (Patients With AML in CR) | Apparent Volume of Distribution During the Terminal Phase (Vz) | 4.85 Litre (l) | Geometric Coefficient of Variation 38.5 |
Secondary
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-infinity)
Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC0-infinity) is presented.
Time frame: At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-infinity) | 23400 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 137 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-infinity) | 97900 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 114 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-infinity) | 296000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 256 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC0-infinity) | 1120000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 39.8 |
Secondary
Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz)
Area under the plasma concentration-time curve over the time interval from zero to the time of the last quantifiable data point (AUC0-tz) is presented.
Time frame: At approximately 5 minutes (min) before start of first (Day 1) and second (Day 8) BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after first and second BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | First infusion | 7730 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 631 |
| BI 836858 (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | Second infusion | 7980 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 417 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | First infusion | 68100 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 89.4 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | Second infusion | 28100 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 133 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | Second infusion | 361000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 32.8 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | First infusion | 190000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 194 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero to the Time of the Last Quantifiable Data Point (AUC0-tz) | First infusion | 807000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 38.1 |
Secondary
Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz)
Area under the plasma concentration-time curve over the time interval of one treatment cycle (AUC0-tz) is presented. One treatment cycle included a first and a second infusion.
Time frame: At approximately 5 minutes (min) before start of first (Day 1) and second (Day 8) BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after first and second BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | first infusion | 7730 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 631 |
| BI 836858 (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | second infusion | 7980 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 417 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | first infusion | 68100 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 89.4 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | second infusion | 28100 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 133 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | second infusion | 361000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 32.8 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | first infusion | 190000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 194 |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Treatment Cycle (AUC0-tz) | first infusion | 807000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 38.1 |
Secondary
Area Under the Plasma Concentration-time Curve Over the Time Interval of One Week (AUC0-168)
Area under the plasma concentration-time curve over the time interval of one week (AUC0-168) after the first infusion is presented.
Time frame: At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs, 72 hrs and 168 hrs after BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Week (AUC0-168) | NA nanograms*hours/millilitre (ng*h/ml) | — |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Week (AUC0-168) | NA nanograms*hours/millilitre (ng*h/ml) | — |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Week (AUC0-168) | NA nanograms*hours/millilitre (ng*h/ml) | — |
| BI 836858 40 mg (Patients With AML in CR) | Area Under the Plasma Concentration-time Curve Over the Time Interval of One Week (AUC0-168) | 783000 nanograms*hours/millilitre (ng*h/ml) | Geometric Coefficient of Variation 37.3 |
Secondary
Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD)
BOR for patients with refractory/relapsed acute myeloid leukemia defined as: -CR:Morphologically leukemia free state/absolute neutrophil count≥1000/microliter(μL)and platelets≥100,000/μL. No transfusion for 1week prior to assessment -CRi:Met criteria for CR, except absolute neutrophils\<1000/μl/platelets\<100,000/μl -PR:Met criteria for CR, except leukemic blasts in bone marrow may range from 5 to 25% as long as count has decreased by at least 50% from pre-study treatment, or\<5% blasts in presence of Auer rods or abnormal morphology -TF:Patient survives≥7 days following completion of initial 2 treatment cycles with persistent leukemia in the last peripheral blood smear or bone marrow or with persistent extramedullary disease - PD:Patient survives\>7 days following completion of initial 2 treatment cycles with increase of blast population in bone marrow or peripheral blood by\>50% or aggravation or new development of extramedullary disease or further deterioration or death due to leukemia
Time frame: From first administration of study drug until the earliest of progressive disease (PD), death or last adequate disease assessment before new anti-cancer therapy, up to 299 days.
Population: Treated Set (TS): TS included patients treated with at least 1 dose of BI 836858. Only patients with relapsed/refractory AML were planned to be analysed for this endpoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | CRi | 0 Participants |
| BI 836858 (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | PD | 8 Participants |
| BI 836858 (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | TF | 3 Participants |
| BI 836858 (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | CR | 0 Participants |
| BI 836858 (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | No assessment post-baseline | 0 Participants |
| BI 836858 (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | Not evaluable | 1 Participants |
| BI 836858 (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | PR | 0 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | TF | 2 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | CR | 0 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | CRi | 0 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | PR | 0 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | PD | 5 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | Not evaluable | 0 Participants |
| BI 836858 40 mg (Patients With AML in CR) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | No assessment post-baseline | 1 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | PD | 3 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | CRi | 0 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | No assessment post-baseline | 1 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | Not evaluable | 1 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | TF | 2 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | PR | 0 Participants |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Best Overall Response According to International Working Group (IWG) Criteria Categorized as CompleteRemission(CR), CR With Incomplete Blood Recovery (CRi), PartialRemission (PR), TreatmentFailure (TF) and ProgressiveDisease (PD) | CR | 0 Participants |
Secondary
Maximum Measured Plasma Concentration (Cmax)
Maximum measured plasma concentration (Cmax) after the first infusion is presented.
Time frame: At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Maximum Measured Plasma Concentration (Cmax) | 873 nanograms per millilitre (ng/ml) | Geometric Coefficient of Variation 207 |
| BI 836858 40 mg (Patients With AML in CR) | Maximum Measured Plasma Concentration (Cmax) | 3270 nanograms per millilitre (ng/ml) | Geometric Coefficient of Variation 35.4 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Maximum Measured Plasma Concentration (Cmax) | 6100 nanograms per millilitre (ng/ml) | Geometric Coefficient of Variation 82.1 |
| BI 836858 40 mg (Patients With AML in CR) | Maximum Measured Plasma Concentration (Cmax) | 9640 nanograms per millilitre (ng/ml) | Geometric Coefficient of Variation 55.7 |
Secondary
Mean Residence Time After Intravenous Infusion (MRT)
Mean residence time after intravenous infusion (MRT) is presented.
Time frame: At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Mean Residence Time After Intravenous Infusion (MRT) | 16.4 hours (hrs) | Geometric Coefficient of Variation 62.1 |
| BI 836858 40 mg (Patients With AML in CR) | Mean Residence Time After Intravenous Infusion (MRT) | 30.8 hours (hrs) | Geometric Coefficient of Variation 85.4 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Mean Residence Time After Intravenous Infusion (MRT) | 50.8 hours (hrs) | Geometric Coefficient of Variation 98.7 |
| BI 836858 40 mg (Patients With AML in CR) | Mean Residence Time After Intravenous Infusion (MRT) | 136 hours (hrs) | Geometric Coefficient of Variation 22.3 |
Secondary
Progression Free Survival for AML Patients in CR With High Risk to Relapse
Progression-free survival was defined as the time from first treatment with BI 836858 until disease progression, relapse or death for AML patients in CR with high risk to relapse.
Time frame: From first treatment with study drug until disease progression, relapse or death for AML patients in CR with high risk to relapse, up to 409 days.
Population: Treated Set (TS): TS included patients treated with at least 1 dose of BI 836858. Only AML patients in CR were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Progression Free Survival for AML Patients in CR With High Risk to Relapse | NA Days |
Secondary
Progression Free Survival for Patients With Refractory or Relapsed Acute Myeloid Leukemia
Progression-free survival was defined as the time from first treatment with BI 836858 until disease progression, relapse or death.
Time frame: From first administration of study drug until progressed according to disease assessment, relapse, or death without progression, up to 167 days.
Population: Treated Set (TS): TS included patients treated with at least 1 dose of BI 836858. Only patients with relapsed/refractory AML were planned to be analysed for this endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Progression Free Survival for Patients With Refractory or Relapsed Acute Myeloid Leukemia | 27.5 Days |
| BI 836858 40 mg (Patients With AML in CR) | Progression Free Survival for Patients With Refractory or Relapsed Acute Myeloid Leukemia | 29.5 Days |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Progression Free Survival for Patients With Refractory or Relapsed Acute Myeloid Leukemia | 50.0 Days |
Secondary
Terminal Half-life (t1/2)
Terminal half-life (t1/2) is presented.
Time frame: At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Terminal Half-life (t1/2) | 11.3 hours (hrs) | Geometric Coefficient of Variation 64.3 |
| BI 836858 40 mg (Patients With AML in CR) | Terminal Half-life (t1/2) | 21.4 hours (hrs) | Geometric Coefficient of Variation 91.7 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Terminal Half-life (t1/2) | 34.5 hours (hrs) | Geometric Coefficient of Variation 107 |
| BI 836858 40 mg (Patients With AML in CR) | Terminal Half-life (t1/2) | 94.3 hours (hrs) | Geometric Coefficient of Variation 22.1 |
Secondary
Time From Dosing to the Maximum Plasma Concentration (Tmax)
Time from dosing to the maximum plasma concentration (tmax) after the first infusion is presented.
Time frame: At 5 minutes (min) before start of BI 836858 infusion and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Time From Dosing to the Maximum Plasma Concentration (Tmax) | 4.43 hours (hrs) |
| BI 836858 40 mg (Patients With AML in CR) | Time From Dosing to the Maximum Plasma Concentration (Tmax) | 6.07 hours (hrs) |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Time From Dosing to the Maximum Plasma Concentration (Tmax) | 5.87 hours (hrs) |
| BI 836858 40 mg (Patients With AML in CR) | Time From Dosing to the Maximum Plasma Concentration (Tmax) | 5.92 hours (hrs) |
Secondary
Time to Treatment Failure for AML Patients in CR With High Risk to Relapse
Time to treatment was defined as the time from first treatment with BI 836858 until disease progression, relapse or death or start of next AML therapy.
Time frame: From first treatment with study drug until disease progression, relapse, death or start of next AML therapy for AML patients in CR with high risk to relapse, up to 409 days.
Population: TS. Only patients in CR were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Time to Treatment Failure for AML Patients in CR With High Risk to Relapse | NA Days |
Secondary
Time to Treatment Failure for Patients With Refractory or Relapsed Acute Myeloid Leukemia
Time to treatment was defined as the time from first treatment with BI 836858 until disease progression, relapse or death or start of next AML therapy.
Time frame: From first administration of study drug until progressive disease, relapse, death or start of next anti-AML therapy, up to 167 days.
Population: Treated Set (TS): TS included patients treated with at least 1 dose of BI 836858. Only patients with relapsed/refractory AML were planned to be analysed for this endpoint.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Time to Treatment Failure for Patients With Refractory or Relapsed Acute Myeloid Leukemia | 27.5 Days |
| BI 836858 40 mg (Patients With AML in CR) | Time to Treatment Failure for Patients With Refractory or Relapsed Acute Myeloid Leukemia | 29.5 Days |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Time to Treatment Failure for Patients With Refractory or Relapsed Acute Myeloid Leukemia | 40.5 Days |
Secondary
Total Plasma Clearance (CL)
Total plasma clearance (CL) is presented.
Time frame: At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Total Plasma Clearance (CL) | 7.11 millilitre/minute (ml/min) | Geometric Coefficient of Variation 137 |
| BI 836858 40 mg (Patients With AML in CR) | Total Plasma Clearance (CL) | 3.40 millilitre/minute (ml/min) | Geometric Coefficient of Variation 114 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Total Plasma Clearance (CL) | 2.25 millilitre/minute (ml/min) | Geometric Coefficient of Variation 256 |
| BI 836858 40 mg (Patients With AML in CR) | Total Plasma Clearance (CL) | 0.595 millilitre/minute (ml/min) | Geometric Coefficient of Variation 39.8 |
Secondary
Volume of Distribution After Intravenous Infusion at Steady State (Vss)
Volume of distribution after intravenous infusion at steady state (Vss) is presented.
Time frame: At 5 minutes (min) before start of the first BI 836858 infusion at Day 1 and at 5 hours (hrs), 6 hrs, 9 hrs, 24 hrs and 72 hrs after the first BI 836858 infusion.
Population: PK parameter analysis set (PKS): This patient set includes all patients in the treated set (TS) who provide at least one pharmacokinetics (PK) parameter.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BI 836858 (Patients With Relapsed\Refractory AML) | Volume of Distribution After Intravenous Infusion at Steady State (Vss) | 7.01 Litre (l) | Geometric Coefficient of Variation 53 |
| BI 836858 40 mg (Patients With AML in CR) | Volume of Distribution After Intravenous Infusion at Steady State (Vss) | 6.30 Litre (l) | Geometric Coefficient of Variation 29.4 |
| BI 836858 40 mg (Patients With Relapsed\Refractory AML) | Volume of Distribution After Intravenous Infusion at Steady State (Vss) | 6.86 Litre (l) | Geometric Coefficient of Variation 69.5 |
| BI 836858 40 mg (Patients With AML in CR) | Volume of Distribution After Intravenous Infusion at Steady State (Vss) | 4.85 Litre (l) | Geometric Coefficient of Variation 39 |