Clinical Trials

Inclusion Criteria:

• Documented diagnosis of MDS according to World Health Organization (WHO) criteria that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease at screening as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC).
  • Phase I dose escalation: patients who experienced ESA treatment failure or do not qualify (serum erythropoietin level > 500 U) for ESA treatment, and are refractory to or not amenable or eligible for established MDS therapy (HMA, lenalidomide).
  • Phase I expansion:
    • Expansion cohort 1 (“pre-treated”): patients who experienced ESA treatment failure or do not qualify (serum erythropoietin level > 500 U) for ESA treatment and are refractory to established MDS therapy (HMA and/or lenalidomide);
    • Expansion cohort 2 (“untreated”): patients who experienced ESA treatment failure or do not qualify (serum erythropoietin level > 500 U) for ESA treatment and who have not received prior HMA and/or lenalidomide (because not amenable or eligible for these treatments).
  • Phase II: patients who experienced ESA treatment failure or do not qualify (serum erythropoietin level > 500 U) for ESA treatment. For definition of further details of the phase II patients to be included the protocol will be amended based on Phase I results.
• Patient has the evidence of symptomatic anemia according to the following criteria:
  • Phase I only: patients must have mean hemoglobin concentration < 10.0 g/dL of 2 measurements (not influenced by RBC transfusion within 7 days of measurement) and having received < 4 units of RBCs within 8 weeks prior to start of treatment; OR
  • Phase I/II: Patients must have received ≥ 2 units of RBCs for hemoglobin ≤ 9.0 g/dL within 8 weeks prior to start of treatment.
• Patient is non-responsive to, refractory to, or intolerant of ESAs, or ESAs are contraindicated or unavailable, or a documented serum erythropoietin level of > 500 U/L.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2 (R14-0080).
• Age ≥ 18 years old.
• Written informed consent which is consistent with International Conference on Harmonization – Good Clinical Practice (ICH-GCP) guidelines and local legislation.

Exclusion Criteria:

• Patient with IPSS category of Int-2 or high-risk MDS.
• Phase II only: Patients with a deletion 5q cytogenetic abnormality.
• Treatment within 28 days prior to Cycle 1 Day 1 with:
  • long acting erythropoiesis stimulating agents;
  • long acting Granulocyte colony-stimulating factor (G-CSF);
  • granulocyte- macrophage colony stimulating factor (GM-CSF);
  • 5-aza, lenalidomide or decitabine;
  • iron chelation and within 14 days prior to Cycle 1 Day 1 with short acting erythropoiesis stimulating agents and short acting G-CSF.
• Patient previously received allogeneic bone marrow or stem cell transplantation.
• Second malignancy currently requiring active therapy (except for hormonal/antihormonal treatment; e.g., in prostate or breast cancer).
• Neutrophils <1000 /μL (1.0 x 109/L).
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) > 2.5 times the upper limit of normal (ULN).
• Bilirubin >1.5 mg/dL, except for Gilbert’s Syndrome or hemolysis.
• Serum creatinine >2.0 mg/dL.
• Known human immunodeficiency virus (HIV) infection and/or active hepatitis B infection (defined as presence of Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA)
• Presence of 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 which in the opinion of the Investigator would limit compliance with trial requirements.
• Patient receiving concomitant therapy, which in the opinion of the Investigator 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; i.e., combination of two forms of effective contraception (defined as hormonal contraception, intrauterine device, transdermal patch, implantable or injectable contraceptive, bilateral tubal ligation etc.).
• Women of childbearing potential are defined as females who:
  • Have experienced menarche;
  • Are not postmenopausal (12 months with no menses without an alternative medical cause);
  • Are not permanently sterilized (e.g., hysterectomy, bilateral oophorectomy or bilateral salpingectomy.
• Male patients with partners of childbearing potential who are unwilling to use condoms in combination with a second effective method of contraception (defined as hormonal contraception, intrauterine device, condom with spermicide, etc.) 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) of first administration of BI 836858, or if the half-life of the previous product is known, within 5 times the half-life, whichever is longer;
  • Patient has persistent toxicities from prior MDS therapies which are determined to be relevant by the Investigator;
  • Concomitant treatment with another investigational agent while participating in this trial.
• Chronic use, as defined by > 2 weeks of a corticosteroid agent that is ≥ 20 mg/day of prednisone or its equivalent, within 4 weeks prior to first administration of BI 836858.
• Treatment with an immunomodulatory agent within 4 weeks prior to first administration of BI 836858.
• Patient received prior treatment with a CD33 antibody.
• In the opinion of the Investigator patient is unable or unwilling to comply with the protocol.