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NCT02240706

Phase I/II Trial to Investigate BI 836858 in Myelodysplastic Syndromes

Terminated Phase 2 Results posted Last updated 21 December 2020
What this trial tests

Phase 2 trial testing Best Supportive Care in Myelodysplastic Syndromes in 27 participants. Terminated before completion.

Timeline
22 January 2015
Primary endpoint
18 November 2019
18 November 2019

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment27
Start date22 January 2015
Primary completion18 November 2019
Estimated completion18 November 2019
Sites5 locations across United States, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

18 and older, any sex, with Myelodysplastic Syndromes. 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.

Number of Patients With Dose Limiting Toxicity (DLT) (Phase I) Primary · From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days

Dose Limiting Toxicity (DLT): * Grade (G) ≥ 3 (CTCAE 4.0), non disease-related, non-hematologic adverse events (AE), except: * Laboratory abnormality, not significant by investigator or resolves spontaneously or can be recovered with appropriate treatment (T) within 5 d * Neutrophils (NP) \<500 /microliters (μL) at T start, febrile neutropenia with NP \<500 /μL or infection with NP \<500 /μL will not constitute a DLT if they can be recovered with appropriate T within 14 d * Inability to deliver study drug full dose according to the assigned dose level within cycle 1 due to drug-related A

GroupValue95% CI
BI 836858 20 mg (Phase I)0
BI 836858 40 mg (Phase I)0
BI 836858 80 mg (Phase I)1
BI 836858 160 mg (Phase I)0
BI 836858 320 mg (Phase I)2
Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase I) Secondary · From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days)

Number of patients with red blood cell (RBC) Transfusion Independency is presented. Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator. A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent. A patient is considered transfusion indepen

GroupValue95% CI
BI 836858 20 mg (Phase I)0
BI 836858 40 mg (Phase I)0
BI 836858 80 mg (Phase I)0
BI 836858 160 mg (Phase I)0
BI 836858 320 mg (Phase I)0
Number of Patients With Hematologic Improvement Neutrophils (HI-N) (Phase I) Secondary · From first administration of BI 836858 until HI-N, up to 168 days (6 cycles, each of 28 days)

Number of patients with hematologic improvement neutrophils (HI-N) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Neutrophil response (HI-N) - Patients with a pretreatment neutrophil count \<1 x 10\^9/liters (L) demonstrate a neutrophil response if they have an at least 100 percent increase and an absolute increase \>0.5 x 10\^9/L.

GroupValue95% CI
BI 836858 20 mg (Phase I)0
BI 836858 40 mg (Phase I)0
BI 836858 80 mg (Phase I)0
BI 836858 160 mg (Phase I)0
BI 836858 320 mg (Phase I)0
Number of Patients With Hematologic Improvement Platelets (HI-P) (Phase I) Secondary · From first administration of BI 836858 until HI-P, up to 168 days (6 cycles, each of 28 days)

Number of patients with hematologic improvement platelets (HI-P) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Platelet response (HI-P) - Patients with a pretreatment platelet count \<100 x 109/Liters (L) demonstrate a platelet response if there is an absolute platelet increase of ≥30 x 109/L for patients starting with \>20 x 109/L platelets. For those with an increase from 10 x 109/L to \>20 x 109/L must have an increase of at least 100 percent.

GroupValue95% CI
BI 836858 20 mg (Phase I)0
BI 836858 40 mg (Phase I)0
BI 836858 80 mg (Phase I)0
BI 836858 160 mg (Phase I)0
BI 836858 320 mg (Phase I)0
Number of Patients With Hematologic Improvement Erythroid (HI-E) (Phase I) Secondary · From first administration of BI 836858 until HI-E, up to 168 days (6 cycles, each of 28 days)

Number of patients with hematologic improvement erythroid (HI-E) is presented. The HI will be evaluated in patients with abnormal pretreatment values defined as follows: Erythroid response (HI-E): Patients with a pretreatment hemoglobin \<11 grams per deciliters (g/dL) demonstrate erythroid response if their hemoglobin increases by ≥1.5 g/dL for at least eight weeks, and there is a reduction in the units of red cell transfusions by an absolute number of at least four red cell transfusions per eight weeks compared with the pretreatment transfusion number in the previous eight weeks. Only red

GroupValue95% CI
BI 836858 20 mg (Phase I)0
BI 836858 40 mg (Phase I)0
BI 836858 80 mg (Phase I)0
BI 836858 160 mg (Phase I)0
BI 836858 320 mg (Phase I)0
Number of Patients With Mean Hemoglobin Increase ≥ 1.5 g/dL (Phase I) Secondary · Up to 48 weeks

Number of patients with mean hemoglobin increase ≥ 1.5 grams per deciliters (g/dL) is presented. Mean hemoglobin increase ≥ 1.5 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.5 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions.

GroupValue95% CI
BI 836858 20 mg (Phase I)0
BI 836858 40 mg (Phase I)0
BI 836858 80 mg (Phase I)0
BI 836858 160 mg (Phase I)1
BI 836858 320 mg (Phase I)0
Number of Patients With Overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] (Phase I) Secondary · From first administration of BI 836858 until overall objective response, up to 168 days (6 cycles, each of 28 days)

Number of patients with overall Objective Response (OR) \[Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)\] is presented. Overall Objective Response is defined as Complete Response (CR), Partial Response (PR), HI-N, HI-P, or HI-E. A patient's " Overall Objective Response " = "Yes" if one of these responses was reported at least once throughout the trial. CR defined as: -Bone marrow: \<5 % blasts with normal maturation of all cell lines (Dysplastic changes should consider the normal range of dysplastic changes), persistent dysplasia will be noted; -Peripheral b

GroupValue95% CI
BI 836858 20 mg (Phase I)0
BI 836858 40 mg (Phase I)0
BI 836858 80 mg (Phase I)0
BI 836858 160 mg (Phase I)0
BI 836858 320 mg (Phase I)0

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of BI 836858 until end of residual effect period (REP), up to 198 days. For all-cause mortality from first administration of BI 836858 until end of follow-up, up to 198 days + 6 months follow-up.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BI 836858 20mg
Serious: 2/3 (67%)
Deaths: 1/3
BI 836858 40mg
Serious: 2/3 (67%)
Deaths: 0/3
BI 836858 80mg
Serious: 3/6 (50%)
Deaths: 1/6
BI 836858 160mg
Serious: 0/4 (0%)
Deaths: 0/4
BI 836858 320mg
Serious: 6/11 (55%)
Deaths: 3/11

Serious adverse events (23 terms)

ReactionSystemBI 836858 20mgBI 836858 40mgBI 836858 80mgBI 836858 160mgBI 836858 320mg
Infusion related reactionInjury, poisoning and procedural complications
Acute coronary syndromeCardiac disorders
Ventricular tachycardiaCardiac disorders
Non-cardiac chest painGeneral disorders
PyrexiaGeneral disorders
CellulitisInfections and infestations
Enterocolitis infectiousInfections and infestations
InfectionInfections and infestations
SepsisInfections and infestations
Staphylococcal infectionInfections and infestations
Wound infectionInfections and infestations
FallInjury, poisoning and procedural complications
Spinal compression fractureInjury, poisoning and procedural complications
Subdural haematomaInjury, poisoning and procedural complications
HyperglycaemiaMetabolism and nutrition disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
SyncopeNervous system disorders
DeliriumPsychiatric disorders
Renal cystRenal and urinary disorders
Lung infiltrationRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
Other adverse events (119 terms — click to expand)

ReactionSystemBI 836858 20mgBI 836858 40mgBI 836858 80mgBI 836858 160mgBI 836858 320mg
Infusion related reactionInjury, poisoning and procedural complications
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Neutrophil count decreasedInvestigations
White blood cell count decreasedInvestigations
Angina pectorisCardiac disorders
DyspepsiaGastrointestinal disorders
StomatitisGastrointestinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
ContusionInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Decreased appetiteMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
HyperglycaemiaMetabolism and nutrition disorders
HyperkalaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Iron overloadMetabolism and nutrition disorders
Bone painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
DysgeusiaNervous system disorders
HeadacheNervous system disorders
AgitationPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
MonocytopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Atrioventricular block first degreeCardiac disorders
PalpitationsCardiac disorders
TachycardiaCardiac disorders
Vision blurredEye disorders
Abdominal discomfortGastrointestinal disorders
Abdominal painGastrointestinal disorders
Anal incontinenceGastrointestinal disorders
ConstipationGastrointestinal disorders
Faeces discolouredGastrointestinal disorders
Gastric ulcerGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders

Most-reported serious reactions: Infusion related reaction, Acute coronary syndrome, Ventricular tachycardia, Non-cardiac chest pain, Pyrexia, Cellulitis, Enterocolitis infectious, Infection.

Data from ClinicalTrials.gov NCT02240706 adverse events section.

Sponsor's own description

Phase I: To investigate maximum tolerated dose (MTD), safety and tolerability, pharmacokinetics, exploratory biomarker and efficacy of BI 836858 monotherapy in patients with low or intermediate-1 risk myelodysplastic syndromes (MDS) with symptomatic anemia. Phase II: To investigate safety and efficacy of BI 836858 plus Best Supportive Care compared to Best Supportive Care alone in low or intermediate-1 risk MDS patients with symptomatic anemia.

Publications & conference data

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

  1. The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes.
    Sallman DA, List A. · · 2019 · cited 202× · PMID 30670444 · DOI 10.1182/blood-2018-10-844654
  2. 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
  3. Novel therapeutic approach to improve hematopoiesis in low risk MDS by targeting MDSCs with the Fc-engineered CD33 antibody BI 836858.
    Eksioglu EA, Chen X, Heider KH, Rueter B, et al · · 2017 · cited 59× · PMID 28096534 · DOI 10.1038/leu.2017.21
  4. Myeloid-Derived Suppressor Cells in Hematologic Diseases: Promising Biomarkers and Treatment Targets.
    Bizymi N, Bjelica S, Kittang AO, Mojsilovic S, et al · · 2019 · cited 47× · PMID 31723807 · DOI 10.1097/hs9.0000000000000168
  5. Treatment of Anemia in Transfusion-Dependent and Non-Transfusion-Dependent Lower-Risk MDS: Current and Emerging Strategies.
    Germing U, Oliva EN, Hiwase D, Almeida A. · · 2019 · cited 36× · PMID 31976486 · DOI 10.1097/hs9.0000000000000314
  6. Bispecific NKG2D-CD3 and NKG2D-CD16 fusion proteins for induction of NK and T cell reactivity against acute myeloid leukemia.
    Märklin M, Hagelstein I, Koerner SP, Rothfelder K, et al · · 2019 · cited 34× · PMID 31142382 · DOI 10.1186/s40425-019-0606-0
  7. Disordered Immune Regulation and its Therapeutic Targeting in Myelodysplastic Syndromes.
    Ivy KS, Brent Ferrell P. · · 2018 · cited 30× · PMID 29934935 · DOI 10.1007/s11899-018-0463-9
  8. Therapeutic Antibodies for Myeloid Neoplasms-Current Developments and Future Directions.
    Schürch CM. · · 2018 · cited 30× · PMID 29868474 · DOI 10.3389/fonc.2018.00152

Verify or expand the search:

Other trials of Best Supportive Care

Trials testing the same drug.

Other recruiting trials for Myelodysplastic Syndromes

Currently open trials in the same condition.

Other Boehringer Ingelheim trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02240706.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing