Study of Clinical Efficacy and Safety of Tosedostat in MDS

Completed · Phase 2

Conditions studied: Myelodysplastic Syndrome

In brief

Study WCMC IST-CTI-MDS evaluates the safety and tolerability of tosedostat in adult patients with pathologically confirmed MDS (\< 20% blasts in bone marrow, peripheral blood, or both) by World Health Organization (WHO) classification after failure of hypomethylating agent-based therapy.

Key facts

Study ID

NCT02452346

Run by

Weill Medical College of Cornell University

People needed

12

Starts

2015-03-20

Expected to finish

2017-10-25

Last updated by the study team

2018-06-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Able to understand and to provide written informed consent
• At least 18 years of age with pathologically confirmed MDS (<20% blasts in bone marrow, peripheral blood, or both) within 6 weeks prior to screening by WHO classification
• Must have received at least 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy and are either refractory to, relapsed after or intolerant to prior therapy with either agent.
• Primary failure/refractory: Stable or worsening disease after a minimum of 4 cycles of decitabine-based or 6 cycles of azacitidine-based therapy
• Secondary failure/relapse: Bone marrow blast count increase or loss of hematologic response after initial treatment response with hypomethylating agent-based therapy
• Intolerance: Intolerance of hypomethylating agent-based therapy regardless of number of cycles completed and clinical response
• Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine treatment per labeling during the past 2 years, defined as follows:
• For patients with <5% BMBL, ≥ 50% increase in BMBL to >5% BMBL
• For patients with 5-10% BMBL, ≥ 50% increase in BMBL to >10% BMBL
• For patients with 10-20% BMBL, ≥ 50% increase in BMBL to >20% BMBL
• For patients with 20-30% BMBL, ≥ 50% increase in BMBL to >30% BMBL
• Any of the following:
• ≥ 50% decrease from maximum remission/response levels in granulocytes or PLT
• Decrease in Hgb concentration by ≥2 g/dL
• Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values < 9 g/dL prior to transfusion to be considered), in the absence of another explanation.
• Has failed to respond to, relapsed following, not eligible, or opted not to participate in BM transplantation
• Patients with very low, low or intermediate risk MDS by the IPSS-R must be transfusion-dependent, with a packed red blood cell requirement of ≥ 2 units/month
• Off azacitidine or decitabine for at least 2 weeks, off all other treatments for MDS for at least 4 weeks. Filgrastim (G-CSF) and EPO are allowed before and during the study as clinically indicated
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Subjects must have adequate hepatic and renal function including the following:
• Total bilirubin ≤ 1.5 x upper limit of normal (in the absence of Gilbert's syndrome)
• AST and ALT ≤ 2.5 x upper limit of normal
• Serum creatinine ≤ 1.5 x upper limit of normal
• Must have acceptable recovery from clinically significant non-hematologic toxicity after prior therapy.
• Must have a life expectancy of at least 2 months

You may not qualify if…

• Presence of AML (≥20% blasts in bone marrow, peripheral blood, or both)
• Presence of serious illness, medical condition, or other medical history, involving the heart, kidney, liver, or other organ system, including abnormal laboratory parameters, which, in the opinion of the Investigator, would be likely to interfere with a subject's participation in the study or with the interpretation of the results.
• Have known active central nervous system disease or active, uncontrolled, clinically significant infection(s)
• Have other active malignancies (including other hematologic malignancies) or other malignancies within 12 months before enrollment, except non-melanoma skin cancer or cervical intraepithelial neoplasia
• Are receiving any other investigational therapy or protocol-prohibited therapy
• Have received previous treatment with tosedostat
• Pregnant or breastfeeding females
• Any prior or co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the subject's participation in the study
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
• Significant* cardiovascular disease defined as:
• Active heart disease including myocardial infarction within 6 months prior to study entry
• Symptomatic coronary artery disease
• Uncontrolled or clinically significant arrhythmia, angina, congestive heart failure
• Presence of clinically significant valvular heart disease
• Presence of clinically significant conduction defect on screening ECG
• Uncontrolled hypertension (i.e., systolic BP >160mmHg, diastolic >90 mmHg in repeated measurements) despite adequate therapy
• Clinically significant atrial fibrillation * Grade 3/4 in the CTCAE v4.0 grading would generally be considered clinically significant, although this remains a judgment for the Investigator to make.
• LVEF ≤ 50%
• Baseline troponin I and b-type natriuretic peptide > Grade I
• Prior exposure cardiotoxic agent, such as anthracycline, within 3 months of enrollment
• Concomitant use of drugs that prolong QT/QTc interval except antibiotics, antifungals, and other antimicrobials used as standard of care for the treatment and prevention of infection and/or other such drugs clinically indicated for patient care. When use of concomitant medications with QT-prolonging potential is necessary, ECG must be repeated 4 hours post-dose on Day 1, on Day 3, and on Day 7, and as clinically indicated, relative to start of agent with QT-prolonging potential.
• Gastrointestinal disorders that may interfere with absorption of drug
• Active serious infection or sepsis
• Clinically significant interstitial lung disease

Where it is running

• Weill Cornell Medical College — New York, New York, United States

Full record on ClinicalTrials.gov

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