BI 836858 Dose Escalation in Patients With Refractory or Relapsed Acute Myeloid Leukemia and in Patients With AML in Complete Remission With High Risk to Relapse
- Registration Number
- NCT01690624
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description BI 836858 20 mg (Patients with relapsed\refractory AML) BI 836858 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). BI 836858 40 mg (Patients with relapsed\refractory AML) BI 836858 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). BI 836858 40 mg (Patients with AML in CR) BI 836858 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. BI836858 10milligram(mg)(Patients with relapsed\refractoryAML) BI 836858 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).
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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
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 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.
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.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.
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.
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.
Trial Locations
- Locations (5)
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States