Clinical Trials /

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

NCT02240706

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.

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Suspended

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Trial to Investigate BI 836858 in Myelodysplastic Syndromes
  • Official Title: A Phase I/II, Multicentre, Open-label, Dose Escalation and Randomized Trial of BI 836858 in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes

Clinical Trial IDs

  • ORG STUDY ID: 1315.7
  • SECONDARY ID: 2018-002177-21
  • NCT ID: NCT02240706

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
BI 836858Arm A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm BActive ComparatorBest Supportive Care Alone
    Arm AExperimentalBI 836858 plus Best Supportive Care
    • BI 836858

    Eligibility Criteria

            Inclusion criteria:
    
              -  Documented diagnosis of Myelodysplastic Syndromes (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 Erythropoiesis-Stimulating
                      Agents (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 (Hypomethylating Agents (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 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.
    
              -  Age >= 18 years.
    
              -  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: i) long acting erythropoiesis
                 stimulating agents, ii) long acting Granulocyte colony-stimulating factor (G-CSF),
                 iii) granulocyte- macrophage colony stimulating factor (GM-CSF), iv) 5-aza,
                 lenalidomide or decitabine, or v) 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).
    
              -  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 and
    
              -  Are not postmenopausal (12 months with no menses without an alternative medical cause)
                 and
    
              -  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 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.
    
                   -  Further exclusion criteria apply
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Phase I: Maximum Tolerated Dose
    Time Frame:up to 4 weeks
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Number of patients with neutrophil response (HI-N)
    Time Frame:up to 6 months
    Safety Issue:
    Description:
    Measure:Time to HI-E response
    Time Frame:up to 6 months
    Safety Issue:
    Description:
    Measure:Duration of Response
    Time Frame:up to 18 months
    Safety Issue:
    Description:
    Measure:Overall objective Response (OR) [Complete Remission (CR), Partial Remission (PR), and Hematologic Improvement (HI)]
    Time Frame:up to 18 months
    Safety Issue:
    Description:
    Measure:Phase I: Number of Patients with red blood cell (RBC) transfusions
    Time Frame:up to 6 months
    Safety Issue:
    Description:
    Measure:Number of patients with erythroid response (HI-E)
    Time Frame:up to 6 months
    Safety Issue:
    Description:
    Measure:Number of patients with platelet response (HI-P)
    Time Frame:up to 6 months
    Safety Issue:
    Description:
    Measure:Mean hemoglobin increase ≥ 1.5 g/dL
    Time Frame:up to 48 weeks
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Boehringer Ingelheim

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