A Phase I/II Clinical Trial of PXD101 in Combination with Idarubicin in Patients with AML Not Suitable for Standard Intensive Therapy

• Conditions: Patients with AML in need of new treatment principles; MedDRA version: 9.1Level: LLTClassification code 10001941Term: AM

• Registration Number: EUCTR2007-000241-35-DE
• Lead Sponsor: TopoTarget A/S

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-04-02
• Last Update Posted: 21 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Inclusion Criteria
1. Signed consent of an IEC-approved informed consent form
2.AML patients evaluable for efficacy:
a. patients above 60 years in first relapse or refractory.
b. patients 18-60 years 2nd relapse or refractory to at least two intensive chemotherapy cycles.
c. patients above 60 years with high risk features (cytogenetics, secondary or treatment related AML)
d) Patients above 60 years with myelodysplastic syndrome with >10% blasts in bone marrow (WHO RAEB-2). For patients below 60 years potential curative treatments should have been exhausted.
3.Performance status (ECOG) = 2
4.Age ³ 18 years
5.Acceptable liver, renal and bone marrow function including the following:
a.Bilirubin £ 1.5 times upper limit of normal (ULN)
b.AST (SGOT) or ALT (SGPT) and Alkaline Phosphatase <3 times upper limit of normal .
c.Serum creatinine <1.5 times upper limit of normal (ULN)
6.Serum potassium within normal range.
7.Acceptable coagulation status: APTT and PT or INR within <1.5 times upper limit of normal or in the therapeutic range if on anticoagulation
8.Female patients with reproductive potential with a negative pregnancy test within the last 7 days before trial enrollment and must use a safe contraceptive during and for a period of 60 days after the trial. Fertile female partners to male participants must likewise use contraceptive

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

6.3.2Exclusion Criteria
1.Treatment with investigational agents within the last 4 weeks
2.Prior treatment with HDAC inhibitors including valproic acid
3.Prior anti-leukemic therapy within the last 3 weeks of trial dosing including chemotherapy, radiotherapy, endocrine therapy or immunotherapy. Cytoreduction with hydroxyurea for high blood counts is allowed during the pre-trial investigation phase but the treatment should be discontinued at least 3 days before the PXD101 treatment.
4.Co-existing active infection (including HIV) or any co-existing medical condition likely to interfere with trial procedures, including significant cardiovascular disease (New York Heart Association Class III or IV cardiac disease), myocardial infarction within the past 6 months, unstable angina, congestive heart failure requiring therapy, unstable arrhythmia or a need for anti-arrhythmic therapy, uncontrolled hypertension, bradycardia with heart rate <50/min or evidence of ischemia on ECG, marked baseline prolongation of QT/QTcF interval, e.g., repeated demonstration of a QTcF interval > 450 msec; long QT Syndrome; the required use of concomitant medication on PXD101 infusion days that may cause Torsade de Pointes. (See Appendix B).
5.Altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures.
6.Concurrent second malignancy.
7.History of hypersensitivity to idarubicin
8.Cumulative idarubicin dose exceeding 100 mg/m2, or a (with respect cardiotoxicity) corresponding dose of other anthracyclines
9.LVEF below normal range (< 45% )
10.Known CNS leukemia

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified