Clinical Trial 17929

Cancer Type: Malignant Hematology
Interventions:BI 836858

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • Rami Komrokji

Overview

Study Title

A Phase I/II, Multicenter, Open-label, Dose Escalation and Randomized Trial of BI 836858 in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes

Summary

The purpose of this research study is to: Identify the maximum tolerated dose; that is, the highest dose of the study drug BI 836858 that does not cause unacceptable side effects, to help determine the dose for the second phase of this study; Obtain information on the safety and effectiveness in participants given BI 836858 alone; Measure and evaluate the behavior of BI 836858 in the blood: pharmacokinetics or PK testing (what the body does to the drug) and pharmacodynamics (what the drug does to the body).

Objective

Phase I: To investigate the 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(BSC) compared to Best Supportive Care alone in low or intermediate-1 risk MDS patients with symptomatic anemia without a deletion 5q cytogenetic abnormality.

Inclusion Criteria

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  • 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 as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC).
  • Evidence of symptomatic anemia according to the following criteria: Phase I only: Participants must have mean hemoglobin concentration = 4 units of RBCs for hemoglobin = 9.0 g/dL within 8 weeks prior to start of treatment.
  • Is nonresponsive to, refractory to, or intolerant of erythropoiesis-stimulating agents (ESAs), or ESAs are contraindicated or unavailable, or a documented serum erythropoietin level of > 500 U/L.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status > 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

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  • IPSS category of Int-2 or high-risk MDS.
  • Phase II only: 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.
  • 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).
  • Prothrombin time (PT) >1.5 x ULN for patients not on therapeutic vitamin K antagonists (phenprocoumon, warfarin).
  • Bilirubin >1.5 mg/dL, except for Gilbert's Syndrome or hemolysis.
  • Serum creatinine >2.0 mg/dL.
  • Known human immunodeficiency virus (HIV) infection or active hepatitis B virus or hepatitis C virus infection. Any serological evidence of current or past hepatitis B exposure unless the serological findings are clearly due to vaccination.
  • 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.
  • 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.
  • Females 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.
  • Males with partners of childbearing potential who are unwilling to use condoms in combination with a second effective method of contraception during the trial and for 6 months after the last administration of BI 836858.
  • Females who are pregnant or nursing.
  • Treatment with another investigational agent under the following conditions: Within 2 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; Potential participant 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.
  • Received prior treatment with a CD33 antibody.
  • In the opinion of the Investigator, unable or unwilling to comply with the protocol.