Testing eltrombopag in patients with acute myelogenous leukemia (AML) who receive chemotherapy with daunorubicin plus cytarabine

Phase 1

Conditions: Acute myelogenous leukemia
MedDRA version: 19.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-000642-20-HU

Lead Sponsor: ovartis Pharma Services AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 120

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following inclusion criteria:
1. Age 18 years and over
2. Diagnosed with AML according to the WHO 2008 classification
? Note: subjects with secondary AML following MDS or secondary to previous leukemogenic therapy are allowed provided that a record of previous MDS history or leukemogenic therapy history is available
3. Eligible for induction by daunorubicin + cytarabine
4. Eligible to give informed consent to participate in the study
5. Have adequate baseline organ function defined by the following criteria:
a. Total bilirubin=<1.5 x upper limit of normal (ULN) except for Gilbert’s syndrome, or other conditions that are not indicative of inadequate liver function (i.e. elevation of indirect bilirubin (haemolytic) in the absence of ALT abnormality)
b. ALT =< 3 x ULN
c. Serum Creatinine =< 2.5 x ULN
6. Adequate cardiac function with LVEF =>50% as assessed by echocardiogram (ECHO) or Multi Gated Acquisition Scan (MUGA)
7. Subjects with a QTc <450msec or <480msec for subjects with bundle branch block The QTc is the QT interval corrected for heart rate according to either Bazett’s formula (QTcB), Fridericia’s formula (QTcF) or another method, machine or manual
overread.
For subject eligibility and withdrawal QTcF will be used.
For purposes of data analysis, QTcF will be used.
The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
8. Women must be either of non-childbearing potential (Refer to Section 7.3.7), or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study (Refer to Section 7.3.7).
9. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in Section 7.3.7 from time of randomization until 30 days after the last dose of investigational product.
10. Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined in Section 7.3.7, during the study and for 30 days following the last dose of
investigational product.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

Subjects meeting any of the following exclusion criteria must not be enrolled in the study:
1. A diagnosis of acute promyelocytic (M3) or acute megakaryocytic leukaemia (M7)
2. Previous history of exposure to an anthracycline compound
3. Previous AML treatment (other than hydroxyurea)
4. Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent
5. History of thromboembolic event or other condition requiring ongoing use of anticoagulation either with warfarin or low molecular-weight heparin
? Note: Occlusion of a central line is not an exclusion
6. Treatment with an investigational drug within 30 days or 5 half lives, whichever is longer, preceding the first dose of study medication
7. Current and continued use during study treatment period of known BCRP inhibitors or known P-gp inhibitors (see Prohibited Medications, Section 6.2) (please see Table 2 in protocol P31.)
8. Known active hepatitis B, hepatitis C or Human immunodeficiency Virus (HIV) nfection
9. Known hypersensitivity to any of the study drugs or its excipients

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the safety and tolerability of eltrombopag versus placebo in subjects receiving standard induction therapy for acute myeloid leukemia (AML);Secondary Objective: Secondary objectives compare the following in subjects treated with eltrombopag versus placebo:<br>? To assess plasma PK parameters of daunorubicin and daunorubicinol<br>? To assess the effects on blood counts including platelets, absolute neutrophil count (ANC), and haemoglobin<br>? To assess the incidence and severity of haemorrhagic events<br>? To assess the effect on AML disease control<br>? To evaluate off-treatment medical resource utilization;Primary end point(s): Safety and tolerability as assessed by adverse events (AE), changes in left ventricular ejection fraction (LVEF) and other safety data including clinical laboratory parameters for eltrombopag-treated subjects versus placebo;Timepoint(s) of evaluation of this end point: The safety endpoint is assessed within 14 days of the remission bone marrow assessment.

Secondary Outcome Measures

Name	Time	Method

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