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

A Phase I, Open-label, Cohort Dose Escalation Trial With BI 836858 in Patients With Refractory or Relapsed Acute Myeloid Leukemia and Patients With Acute Myeloid Leukemia in Complete Remission With High Risk to Relapse.

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: BI 836858

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: BI 836858; Monotherapy with BI 836858 administered as intravenous infusion
Experimental: 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).	Drug: BI 836858; Monotherapy with BI 836858 administered as intravenous infusion
Experimental: 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).	Drug: BI 836858; Monotherapy with BI 836858 administered as intravenous infusion
Experimental: 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.	Drug: BI 836858; Monotherapy with BI 836858 administered as intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the Maximum Tolerated Dose (MTD) of BI 836858	This trial was discontinued prior to reaching the primary endpoint of determining MTD.	From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.
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).	From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.
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.	From first administration of study drug until progressed according to disease assessment, relapse, or death without progression, up to 167 days.
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.	From first administration of study drug until progressive disease, relapse, death or start of next anti-AML therapy, up to 167 days.
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.	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.
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.	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.
Maximum Measured Plasma Concentration (Cmax)	Maximum measured plasma concentration (Cmax) after the first infusion is presented.	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)	Time from dosing to the maximum plasma concentration (tmax) after the first infusion is presented.	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.
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.	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 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.	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 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.	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)	Terminal half-life (t1/2) is presented.	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)	Mean residence time after intravenous infusion (MRT) is presented.	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)	Total plasma clearance (CL) is presented.	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)	Apparent volume of distribution during the terminal phase (Vz) is presented.	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)	Volume of distribution after intravenous infusion at steady state (Vss) is presented.	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 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.	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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2012
• Primary Completion (Actual): May 21, 2018
• Study Completion (Actual): May 21, 2018

Study Registration Dates

• First Submitted: September 13, 2012
• First Submitted That Met QC Criteria: September 19, 2012
• First Posted (Estimated): September 24, 2012

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Disease Progression; Pathologic Complete Response; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 1315.1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to:

https://www.mystudywindow.com/msw/datatransparency