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

NCT01690624 | Completed Phase 1 Results

• 1 other identifier: 1315.1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (16)

• 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.

• 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.

• 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.

• 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.

• 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.

Study Arms (4)

BI836858 10milligram(mg)(Patients with relapsed\refractoryAML)

EXPERIMENTAL

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

BI 836858 20 mg (Patients with relapsed\refractory AML)

EXPERIMENTAL

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

BI 836858 40 mg (Patients with relapsed\refractory AML)

EXPERIMENTAL

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

BI 836858 40 mg (Patients with AML in CR)

EXPERIMENTAL

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

Interventions

BI 836858 DRUG

Monotherapy with BI 836858 administered as intravenous infusion

BI 836858 20 mg (Patients with relapsed\refractory AML); BI 836858 40 mg (Patients with AML in CR); BI 836858 40 mg (Patients with relapsed\refractory AML); BI836858 10milligram(mg)(Patients with relapsed\refractoryAML)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (5)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

BI 836858

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Discontinuation of prior anti-leukemia therapy was required at least 2 weeks before first administration of trial drug.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Centre
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 24, 2012
• Study Start: September 13, 2012
• Primary Completion: May 21, 2018
• Study Completion: May 21, 2018
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)