A study in patients with Myelodysplastic Syndromes

Phase 1

Conditions: Myelodysplastic Syndromes
Therapeutic area: Diseases [C] - Cancer [C04]
MedDRA version: 17.1Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851

Registration Number: EUCTR2013-003235-30-DE

Lead Sponsor: Eli Lilly and Company

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 140

Inclusion Criteria

[1] have a confirmed diagnosis of MDS based on the WHO criteria. Patients with 5q deletions are allowed only if they have failed or are intolerant to lenalidomide treatment. Patients with WHO diagnosis of nonproliferative MDS/myeloproliferative neoplasms are also included.
[2] have IPSS-R category of very low-, low-, or intermediate-risk disease as confirmed by
• bone marrow examination during screening period (will be used also for the correlative/exploratory studies)
•=10% marrow blasts
•appropriate calculation of their IPSS-R score that is not influenced by rise of haematology scores by prior infusions (eg, by reviewing the transfusion history and associated Hb levels prior to each transfusion during the 8 weeks prior to the screening period)
[3] meet the following haematologic criteria 8 weeks prior to registration (according to the IWG criteria):
• Phase 2: anaemia with Hb =10.0 g/dL (based on the average of 2 baseline measurements and untransfused for at least 1 week) with or without RBC transfusion dependence confirmed for a minimum of 8 weeks before enrolment (eg, transfusion dependency defined by at least 4 units of RBC administered within 8 weeks before baseline).
•Phase 3: anaemia with RBC transfusion dependence confirmed within 8 weeks before enrolment (eg, transfusion dependency defined by at least 4 units of RBC administered within 8 weeks before date of enrolment).
[4] have a performance status of =2 on the Eastern Cooperative Oncology Group (ECOG) scale.
[5] have discontinued all disease-modifying therapy for MDS, including investigational treatments, for 28 days prior to initiation of study treatment, with the exception of transfusions and the following supportive care:
• Patients may receive prophylactic steroids (such as prednisolone, methylprednisolone, or dexamethasone) to prevent transfusion reactions.
• Iron chelation therapy is allowed if started prior to enrolment and patients have been stable for at least 3 months.
• Granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) is allowed in the presence of neutropaenic fever or documented neutropaenic infection.
• Patients may have been treated with danazol or prior hypomethylating agents
[6] have adequate hepatic function, defined as bilirubin =1.5 x the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels =2.5 x ULN
[7] have adequate renal function, defined as serum creatinine levels =2.0 x ULN
[8] are at least 18 years old at the time of screening
[9] use an approved contraceptive method (for example, intrauterine device, birth control pills, or barrier device), if appropriate (male and female patients with reproductive potential) during and for 6 months after discontinuation of study treatment
• Women of childbearing potential must have a negative beta-human chorionic gonadotropin pregnancy test documented within 7 days prior to treatment. If condoms are used as a barrier contraceptive, a spermicidal agent should be added to ensure that pregnancy does not occur. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
[10] have given written informed consent/assent prior to any study-specific procedures
[11] are able to swallow tablets
[12] are willing and able to comply with protocol procedures (including completion of diaries

Exclusion Criteria

[14] have moderate or severe cardiovascular disease:
• have the presence of cardiac disease, including a myocardial infarction within 6 months prior to study entry, unstable angina pectoris, New York Heart Association Class III/IV congestive heart failure, or uncontrolled hypertension.
• have documented major ECG abnormalities (not responding to medical treatments).
• have major abnormalities documented by ECHO with Doppler (for example, moderate or severe heart valve function defect and/or left ventricular [LV] ejection fraction <50%, evaluation based on the institutional lower limit of normal). For additional details, refer to the attached ECHO protocol (Attachment 9).
• have predisposing conditions that are consistent with development of aneurysms of the ascending aeorta or aeortic stress (for example, family history of aneurysms, Marfan-Syndrome, bicuspid aeortic valve, evidence of damage to the large vessels of the heart documented by CT scan/MRI with contrast)
[15] have previous history of AML
[16] are women who are pregnant or lactating
[17] have a serious concomitant systemic disorder including active infection with hepatitis B virus (positive hepatitis B surface antigen [+HBsAg]), hepatitis C virus (HCV), and human immunodeficiency virus (HIV)
[18] have a second primary malignancy that, in the judgment of the investigator and Lilly, may affect the interpretation of results
[19] have prior malignancies. Patients with carcinoma in situ of any origin and patients with prior malignancies who are in remission and whose likelihood of recurrence is very low (such as basal cell carcinoma), as judged by the Lilly clinical research physician (CRP), are eligible for this study. The Lilly CRP will approve enrolment of patients with prior malignancies in remission before these patients are enrolled.
[20] are unwilling or unable to participate in, or do not have tissue adequate for participation in, the translational research portion of the study. Patients with inadequate tissue are ineligible for this study.
[21] are currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the study drug/device used in this study) or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
[22] have untreated hypothyroidism as determined by the investigator
[23] have received ESAs within 28 days prior to enrolment
[24] are receiving immunosuppressive agents (eg, cyclosporine) except for corticosteroids for transfusions