A phase Ib, open-label, multi-center dose-finding study of oral panobinostat (LBH589) in combination with ara-C and mitoxantrone as salvage therapy for refractory or relapsed acute myeloid leukemia - N/A
- Conditions
- refractory or relapsed acute myeloid leukemiaMedDRA version: 9.1Level: LLTClassification code 10000886Term: Acute myeloid leukemia
- Registration Number
- EUCTR2008-002986-30-FR
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 26
Patients with cytopathologically confirmed diagnosis of AML according to
WHO criteria
Relapsed after receiving up to 1 prior induction regimens (first relapse) or
patients who are refractory (no CR) to not more than one prior combination
chemotherapy induction regimen.
Age more than 18 years
ECOG performance status = 2
Patients must have the following laboratory values unless considered due to
leukemia: AST/SGOT and/or ALT/SGPT = 2.5 x ULN; Serum creatinine = 1.5
x ULN or GFR = 60 mL/min; Total and direct serum bilirubin = 1.5 x ULN;
electrolyte panel within normal ranges for the institution unless attributed to
the underlying disease.
Eligible for ara-C and mitoxantrone chemotherapy
Written informed consent obtained prior to any screening procedures
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
Subjects with Acute Promyelocytic Leukemia (APL)
Concurrent therapy with any other investigational agent
Patients who received more than maximal two chemotherapy induction cycles
and four chemotherapy consolidation cycles for their AML disease
CNS involvement
Female patients who are pregnant or breast feeding or patients of
childbearing potential (WOCBP) not willing to use a double barrier method of
contraception during the study and for 3 months following the last dose of
study drug.
Male patients whose sexual partner(s) are women of childbearing potential
who are not willing to use a double barrier method of contraception, one of
which includes a condom, during the study and for 3 months after the end of
treatment.
Prior treatment with deacetylase inhibitors
Patients who have received cumulative doses of = 360 mg/m2 of doxorubicin
(or its equivalent to other anthracyclines, e.g. 225 mg/m2 of idarubicin, 900
mg/m2 of daunorubicin, 140 mg/m2 of mitoxantrone, 450 mg/m2 of pegylated
liposomal doxorubicin hydrochloride).
Any of concurrent severe and/or uncontrolled medical conditions which could
compromise participation in the study. For example:
Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular
tachyarrhythmia, clinically significant resting bradycardia (<50 beats per
minute), QTcF > 460 ms on screening ECG, or right bundle branch block +
left anterior hemiblock (bifascicular block)
Presence of unstable atrial fibrillation (ventricular response rate >100 bpm).
Patients with stable atrial fibrillation are eligible provided they do not meet the
other cardiac exclusion criteria
Previous history of angina pectoris or acute MI within 6 months
Baseline LVEF <45% by echocardiography
Other clinically significant heart disease (e.g. uncontrolled hypertension or
history of poor compliance with an antihypertensive regimen)
Uncontrolled diabetes
Active or uncontrolled infection
Uncontrolled hypothyroidism
Acute or chronic liver or renal disease
Impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral panobinostat (e.g., ulcerative
diseases, diarrhea, malabsorption syndrome, or small bowel resection)
Time windows for prior therapies:
All acute toxic effects of any prior therapy of leukemic disease must have
resolved to National Cancer Institute (NCI) Common Terminology Criteria for
Adverse Events (CTCAE, Version 3.0) Grade <2 (with exception of
chemotherapy-induced alopecia)
Last dose of prior chemotherapy, immunotherapy or investigational agent no
less than 14 days prior to receipt of study medication and have recovered at
least CTCAE Grade <2, except for hydroxyurea which must be finished 48
hours before first administration.
Wide field radiotherapy = 4 weeks or limited radiation for palliation = 2 weeks
prior to starting the study treatment or who have not recovered from side
effects of such therapy
Drugs which may cause QT prolongation and the treatment cannot be
discontinued or switched to a different medication prior to starting study drug.
HIV, Hepatitis B/C infection according to the medical history (testing will not
be performed)
Unwilling or unable to comply with the protocol
Inability to swallow capsules
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the maximum-tolerated dose (MTD) in terms of the incidence of<br>dose-limiting toxicity (DLT) of panobinostat in combination with ara-C and<br>mitoxantrone at a fixed dose in adult patients with relapsed or is primary<br>refractory acute myeloid leukemia (AML).;Secondary Objective: Dose escalation and expansion part:<br>To assess the safety profile of panobinostat in combination with ara-C and<br>mitoxantrone in this patient population during the escalation and expansion<br>phase (at MTD) of the study.<br>;Primary end point(s): Dose escalation part:<br>Incidence of DLT
- Secondary Outcome Measures
Name Time Method