NCT02632721

A Trial to Find and Investigate a Safe Dose of BI 836858 in Combination With Decitabine for Patients With Acute Myeloid Leukemia (AML)

Completed Phase 1, PHASE2 Results posted Last updated 19 March 2024

What this trial tests

Phase 1, PHASE2 trial testing Decitabine in Leukemia, Myeloid, Acute in 49 participants. Completed in 16 January 2023.

Timeline

16 June 2016

Primary endpoint
16 January 2023

16 January 2023

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	49
Start date	16 June 2016
Primary completion	16 January 2023
Estimated completion	16 January 2023
Sites	14 locations across Italy, United States, Germany, Spain

Drugs / interventions tested

• Decitabine (decitabine) — full drug profile →
• BI 836858 — full drug profile →

Conditions studied

• Leukemia, Myeloid, Acute — all drugs for Leukemia, Myeloid, Acute →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Leukemia, Myeloid, Acute. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase I: Number of Patients With Dose Limiting Toxicity (DLT(s)) During First Treatment Cycle Primary · Up to 28 days (first treatment cycle).

Number of patients with dose limiting toxicity (DLT(s)) for BI 836858 in combination with decitabine during first treatment cycle (Phase 1). DLT was defined as any non-disease-related non-haematological adverse event (AE) of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher. Expected non-haematological disease-related AEs were not to be regarded as a DLT. These included complications resulting from haematological AEs such as: * Bleeding and complications from bleeding due to thrombocytopenia as defined by the Investigator, * Infection and complications from infections

Group	Value	95% CI
Phase I Dose Escalation: BI 836858 20 mg + Decitabine (Intensive)	0
Phase I Dose Escalation: BI 836858 40 mg + Decitabine (Intensive)	0
Phase I Dose Escalation: BI 836858 80 mg + Decitabine (Intensive)	0
Phase I Extension A: BI 836858 80 mg + Decitabine (Intensive)	1
Phase I Extension B: BI 836858 80 mg + Decitabine (Standard)	1

Phase I: Maximum Tolerated Dose (MTD) of BI 836858 in Combination With Decitabine Primary · From first drug administration until end of treatment, up to 941 days.

The Maximum tolerated dose (MTD) of BI 836858 in combination with decitabine was estimated after the dose escalation part of the trial obtaining on the basis of dose limiting toxicities (DLT(s)) observed during the first treatment cycle. However, for those patients who receive more than one cycle of the combination treatment, all adverse events that constitute a DLT will be considered for re-estimation of the MTD based on the Bayesian logistic regression model (BLRM). The MTD is defined as the highest dose of BI 836858 (in combination with decitabine) with less than 25% risk of the true DLT ra

Group	Value	95% CI
Phase I: BI 836858 + Decitabine	NA

Phase 1: Number of Patients With Objective Response (CR + CRi) Secondary · From start of treatment until the earliest of progression, death or end of trial, up to 971 days.

Number of patients with objective response (Complete remission (CR) + complete remission with incomplete remission (CRi)). CR was defined as bone marrow (BM) blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count \> 1.0 x 109/L \[1,000/μL\]; platelet count \> 100 x 109/L \[100,000/μL\]; independence of red blood cells transfusions (no transfusion for 1 week prior to the assessment). No minimum duration of response is required. CRi was defined as all CR criteria except for residual neutropenia (\< 1.0 x 109/L \[1,000/μL\]) or thrombocytope

Objective response (CR + CRi)

Group	Value	95% CI
Phase I Dose Escalation: BI 836858 20 mg + Decitabine (Intensive)	2
Phase I Dose Escalation: BI 836858 40 mg + Decitabine (Intensive)	0
Phase I Dose Escalation: BI 836858 80 mg + Decitabine (Intensive)	6
Phase I Extension A: BI 836858 80 mg + Decitabine (Intensive)	7
Phase I Extension B: BI 836858 80 mg + Decitabine (Standard)	4

Complete remission (CR)

Group	Value	95% CI
Phase I Dose Escalation: BI 836858 20 mg + Decitabine (Intensive)	1
Phase I Dose Escalation: BI 836858 40 mg + Decitabine (Intensive)	0
Phase I Dose Escalation: BI 836858 80 mg + Decitabine (Intensive)	1
Phase I Extension A: BI 836858 80 mg + Decitabine (Intensive)	3
Phase I Extension B: BI 836858 80 mg + Decitabine (Standard)	3

Complete remission with incomplete recovery (CRi)

Group	Value	95% CI
Phase I Dose Escalation: BI 836858 20 mg + Decitabine (Intensive)	1
Phase I Dose Escalation: BI 836858 40 mg + Decitabine (Intensive)	0
Phase I Dose Escalation: BI 836858 80 mg + Decitabine (Intensive)	5
Phase I Extension A: BI 836858 80 mg + Decitabine (Intensive)	4
Phase I Extension B: BI 836858 80 mg + Decitabine (Standard)	1

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of trial medication until 30 days of residual effect period after the last administration of trial medication, up to 971 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I Dose Escalation: BI 836858 20 mg + Decitabine (Intensive)

Serious: 4/4 (100%)

Deaths: 3/4

Phase I Dose Escalation: BI 836858 40 mg + Decitabine (Intensive)

Serious: 3/3 (100%)

Deaths: 2/3

Phase I Dose Escalation: BI 836858 80 mg + Decitabine (Intensive)

Serious: 8/9 (89%)

Deaths: 5/9

Phase I Extension A: BI 836858 80 mg + Decitabine (Intensive)

Serious: 14/15 (93%)

Deaths: 11/15

Phase I Extension B: BI 836858 80 mg + Decitabine (Standard)

Serious: 17/18 (94%)

Deaths: 13/18

Serious adverse events (61 terms)

Reaction	System	Phase I Dose Escalation: B…	Phase I Dose Escalation: B…	Phase I Dose Escalation: B…	Phase I Extension A: BI 83…	Phase I Extension B: BI 83…
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—
Bronchopulmonary aspergillosis	Infections and infestations	—	—	—	—	—
Device related infection	Infections and infestations	—	—	—	—	—
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—	—
Tumour lysis syndrome	Metabolism and nutrition disorders	—	—	—	—	—
Renal failure	Renal and urinary disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Disseminated intravascular coagulation	Blood and lymphatic system disorders	—	—	—	—	—
White blood cell disorder	Blood and lymphatic system disorders	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—
Atrioventricular block complete	Cardiac disorders	—	—	—	—	—
Cardiac arrest	Cardiac disorders	—	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—	—
Tachyarrhythmia	Cardiac disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Enteritis	Gastrointestinal disorders	—	—	—	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—	—	—	—
General physical health deterioration	General disorders	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—
Non-cardiac chest pain	General disorders	—	—	—	—	—

Other adverse events (272 terms — click to expand)

Reaction	System	Phase I Dose Escalation: B…	Phase I Dose Escalation: B…	Phase I Dose Escalation: B…	Phase I Extension A: BI 83…	Phase I Extension B: BI 83…
Infusion related reaction	Injury, poisoning and procedural complications	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—
Gamma-glutamyltransferase increased	Investigations	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—
Syncope	Nervous system disorders	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—
Haematoma	Vascular disorders	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—	—
Vertigo	Ear and labyrinth disorders	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—
Haemorrhoids	Gastrointestinal disorders	—	—	—	—	—

Most-reported serious reactions: Febrile neutropenia, Malignant neoplasm progression, Pneumonia, Pyrexia, Sepsis, Bronchopulmonary aspergillosis, Device related infection, Infusion related reaction.

Data from ClinicalTrials.gov NCT02632721 adverse events section.

Sponsor's own description

Phase I Dose Escalation:

Primary objective is to determine the Maximum Tolerated Dose (MTD) and the recommended dose for Phase I Extension.

Secondary objective is to investigate the safety, pharmacokinetics and efficacy of BI 836858 in combination with decitabine

Phase I Extension:

Primary objective is to collect additional data on safety, pharmacokinetics and efficacy and to define the Recommended Phase II Dose (RP2D) of BI 836858 in combination with decitabine.

Phase II: Primary objective is to investigate efficacy, safety and pharmacokinetics of BI 836858 in combination with decitabine compared to decitabine monotherapy.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Unleashing Natural Killer Cells in the Tumor Microenvironment-The Next Generation of Immunotherapy?
   Ben-Shmuel A, Biber G, Barda-Saad M. · · 2020 · cited 103× · PMID 32153582 · DOI 10.3389/fimmu.2020.00275
2. Natural killer cell-based immunotherapy for acute myeloid leukemia.
   Xu J, Niu T. · · 2020 · cited 83× · PMID 33287858 · DOI 10.1186/s13045-020-00996-x
3. Antibody Therapies for Acute Myeloid Leukemia: Unconjugated, Toxin-Conjugated, Radio-Conjugated and Multivalent Formats.
   Williams BA, Law A, Hunyadkurti J, Desilets S, et al · · 2019 · cited 43× · PMID 31434267 · DOI 10.3390/jcm8081261
4. Therapeutic Antibodies for Myeloid Neoplasms-Current Developments and Future Directions.
   Schürch CM. · · 2018 · cited 30× · PMID 29868474 · DOI 10.3389/fonc.2018.00152
5. Antibody therapies for the treatment of acute myeloid leukemia: exploring current and emerging therapeutic targets.
   Morse JW, Rios M, Ye J, Rios A, et al · · 2023 · cited 10× · PMID 36762937 · DOI 10.1080/13543784.2023.2179482
6. Monoclonal Antibodies Against Myeloid Leukemia Cells: Current Knowledge and Future Directions.
   Damiani D, Tiribelli M. · · 2025 · cited 2× · PMID 40429716 · DOI 10.3390/ijms26104571
7. Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.
   Guo X, Yu S, Ren X, Li L. · · 2023 · cited 2× · PMID 37810157 · DOI 10.1016/j.heliyon.2023.e19222
8. Revolutionizing acute myeloid leukemia treatment: a systematic review of immune-based therapies.
   Ebinama U, George B. · · 2025 · cited 1× · PMID 39864030 · DOI 10.1007/s12672-025-01797-9