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Leukemia, Myeloid, AcutePhase 1NCT01690624

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 1 study testing BI 836858 in people with Leukemia, Myeloid, Acute, run by Boehringer Ingelheim at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia, Myeloid, Acute
What is being tested?
BI 836858
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
5 sitesUnited States
Study dates
13 Sep 2012to 21 May 2018
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • Eastern Cooperative Oncology Group Performance Status 0, 1 or 2
  • Age 18 years or older
  • Written informed consent which is consistent with International Conference on Harmonization, Good Clinical Practice (ICH-GCP) guidelines and local legislation.

Who cannot join

  • Patients with acute promyelocytic leukemia according to WHO definition.
  • Patients with refractory or relapsed acute myeloid leukemia > 5.000 blasts in the peripheral blood.
  • 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.
  • 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.
  • Patients who are candidates for allogeneic stem cell transplantation (for patients with refractory or relapsed acute myeloid leukemia).
  • Second malignancy currently requiring active therapy.
Show all 24Show fewer
  • Symptomatic central nervous system involvement
  • 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.
  • Prothrombin time (PT) >1.5 x ULN for subjects not on therapeutic vitamin K antagonists (phenprocoumon, warfarin)
  • 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.
  • Serum creatinine greater than 2.0 mg/dl
  • Known human immunodeficiency virus (HIV) infection or active hepatitis B virus or hepatitis C virus infection.
  • 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
  • Psychiatric illness or social situation that would limit compliance with trial requirements
  • Concomitant therapy, which is considered relevant for the evaluation of the efficacy or safety of the trial drug
  • 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
  • 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
  • Pregnant or nursing female patients
  • Treatment with another investigational agent under the following conditions:
  • Within two weeks (4 weeks for biologics or 5 half-lives, whichever is longer) of first administration of BI 836858; or
  • Patient has persistent toxicities from prior anti-leukemic therapies which are determined to be relevant by the Investigator.
  • Concomitant treatment with another investigational agent while participating in this trial.
  • Prior treatment with a CD33 antibody
  • Patient unable or unwilling to comply with the protocol.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

  • Northwestern University

    Chicago, Illinois, 60611

  • The Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: 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.

Being tested
BI 836858
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BI 836858Drug

    Monotherapy with BI 836858 administered as intravenous infusion

Study groups in NCT01690624
Study groupRoleWhat they receive
BI836858 10milligram(mg)(Patients with relapsed\refractoryAML)ExperimentalPatients 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).
Receives: Drug: BI 836858
BI 836858 20 mg (Patients with relapsed\refractory AML)ExperimentalPatients 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).
Receives: Drug: BI 836858
BI 836858 40 mg (Patients with relapsed\refractory AML)ExperimentalPatients 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).
Receives: Drug: BI 836858
BI 836858 40 mg (Patients with AML in CR)ExperimentalPatients 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.
Receives: Drug: BI 836858

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Determination of the Maximum Tolerated Dose (MTD) of BI 836858

    This trial was discontinued prior to reaching the primary endpoint of determining MTD.

    Measured: From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.

  2. 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).

    Measured: From the first administration of BI 836858 to start of the fifth administration, excluding the day of fifth administration, up to 28 days.

Secondary outcomes (16)

  1. 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

    Measured: 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.

  2. 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.

    Measured: From first administration of study drug until progressed according to disease assessment, relapse, or death without progression, up to 167 days.

  3. 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.

    Measured: From first administration of study drug until progressive disease, relapse, death or start of next anti-AML therapy, up to 167 days.

  4. 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.

    Measured: 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.

  5. 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.

    Measured: 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.

  6. Maximum Measured Plasma Concentration (Cmax)

    Maximum measured plasma concentration (Cmax) after the first infusion is presented.

    Measured: 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.

  7. Time From Dosing to the Maximum Plasma Concentration (Tmax)

    Time from dosing to the maximum plasma concentration (tmax) after the first infusion is presented.

    Measured: 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.

  8. 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.

    Measured: 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.

  9. 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.

    Measured: 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.

  10. 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.

    Measured: 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.

  11. Terminal Half-life (t1/2)

    Terminal half-life (t1/2) is presented.

    Measured: 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.

  12. Mean Residence Time After Intravenous Infusion (MRT)

    Mean residence time after intravenous infusion (MRT) is presented.

    Measured: 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.

  13. Total Plasma Clearance (CL)

    Total plasma clearance (CL) is presented.

    Measured: 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.

  14. Apparent Volume of Distribution During the Terminal Phase (Vz)

    Apparent volume of distribution during the terminal phase (Vz) is presented.

    Measured: 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.

  15. Volume of Distribution After Intravenous Infusion at Steady State (Vss)

    Volume of distribution after intravenous infusion at steady state (Vss) is presented.

    Measured: 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.

  16. 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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Sep 2012 (estimated)
  2. Study start13 Sep 2012
  3. Primary completion21 May 2018
  4. Study completion21 May 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01690624
Sponsor's protocol ID
1315.1
Status last verified
Dec 2024
First submitted
13 Sep 2012
Last updated
27 Jan 2025
Individual data sharing
No: 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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 836858 in people with Leukemia, Myeloid, Acute, run by Boehringer Ingelheim at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determination of the Maximum Tolerated Dose (MTD) of BI 836858 (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01690624.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.

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