A Phase II Study of Oral Single Agent Panobinostat in Patients with Refractory de novo or secondary Acute Myelogenous Leukemia (AML) - N/A

• Conditions: Patients with refractory de novo or secondary acute myelogenous leukemia (AML); MedDRA version: 9.1Level: LLTClassification code 10000886Term: Acute myeloid leukemia

• Registration Number: EUCTR2008-002983-32-GR
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-19
• Last Update Posted: 3 December 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 164

Inclusion Criteria

5.1.1 Stratum A Specific Inclusion Criterion
1. Refractory AML with confirmed initial diagnosis of de novo AML (excluding APL)
5.1.2 Stratum B Specific Inclusion Criterion
Refractory AML with confirmed initial diagnosis of AML (excluding APL) secondary to
AHD or MDS with either condition precedent to AML (MDS/AHD) having received either no
treatment or conventional care regimens (CCR), including best supportive care (BSC), low
dose cytarabine, intensive chemotherapy, hypomethylating agents (azacitidine, decitabine), or
other therapies (e.g. lenalidomide)
5.1.3 Stratum A or B General Inclusion Criteria
1. Written informed consent prior to study-specific screening procedures
2. Age = 18 years old
3. Refractory AML, defined as no response (CR1) to initial induction treatment or CR1
lasting <12 months and in first relapse
4. Eastern Cooperative Group (ECOG) performance status = 2
5. Laboratory values as follows:
• Electrolyte panel WNL for the institution (potassium and magnesium values < lower
limit of normal must be corrected to WNL prior to dosing)
• Total calsium (corrected for albumin) or ionized calcium WNL for the institution
• AST/SGOT and ALT/SGPT = 2.5 x ULN (NCI CTCAE Gr 1)
• Serum creatinine = 1.5 x ULN (NCI CTCAE Gr 1)
• Serum bilirubin = 1.5 x ULN unless attributed to underlying disease (NCI CTCAE Gr
1)
• INR = 1.5 and PTT WNL. Patients receiving anticoagulation therapy (e.g. coumadin,
heparin) are eligible provided anticoagulation therapy can be discontinued or changed
to parenteral medications while the platelet count is less than 50,000/mm3
• Negative serum pregnancy test (within 7 days of first dose)
• Negative urine pregnancy test immediately prior to first dose
• Clinically euthyroid (hypothyroidism corrected with supplementation is permitted)
6. Patient has received remission induction therapy (± consolidation) for AML, including
chemotherapy and/or HSCT.
7. Previous chemotherapy for AML has stopped at least 2 weeks or at least five half lives,
whichever is longer, before the first dose of study drug
8. Patient has recovered from toxicity of previous antileukemic therapy, including Grade = 1
non-hematologic toxicity prior to the first dose of study drug
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

5.1.4 Stratum A or B General Exclusion Criteria
1. Patients with initial diagnosis of AML secondary to ionizing radiation/cytotoxic therapy
(e.g. alkylating agents) for previous malignancy
2. Patients requiring valproic acid for any medical condition during the study or within 5
days prior to the first dose of study drug
3. Clinical symptoms suggesting CNS leukemia (patients with neurologic symptoms must
undergo lumbar puncture and a CT scan or MRI of the brain to exclude CNS involvement
4. Patients receiving supportive therapy related to complications of allogeneic
transplantation, including infections or GVH directed therapy
5. Patients who have received either hydroxyurea or glucocorticosteroids for prevention of
leukostasis less than 24 hours before the fist dose of study drug
6. Patients with another malignancy (with the exception of prior MDS in patients with initial
diagnosis of AML secondary to MDS/AHD) unless disease-free for at least 3 years
following the completion of curative intent therapy. Patients with treated non-melanoma
skin cancer, in situ carcinoma, or cervical intraepithelial neoplasm regardless of the
disease-free duration, are eligible if definitive treatment for the condition has been
completed.
7. Patients with impaired cardiac function including any of the following:
• Complete left bundle branch block or use of a permanent cardiac pacemaker,
congenital long QT syndrome, history or presence of ventricular tachyarrhythmias,
clinically significant resting bradycardia (<50 beats per minute), QTcF = 450 ms on
screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular
block)
• LVEF< lower limit of institutional normal, as assessed by ECHO or MUGA
• 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
• Angina pectoris or acute MI within 6 months
• Other clinically significant heart disease (e.g. uncontrolled hypertension or history of
poor compliance with an antihypertensive regimen)
8. Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled
diabetes mellitus, chronic obstructive or chronic restrictive pulmonary disease including
dyspnea at rest from any cause) or history of serious organ dysfunction or disease
involving the heart, kidney or liver and/or known seropositive HIV (HIV screening testing
is not required)
9. Patient has an impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral panobinostat (e.g., ulcerative disease,
uncontrolled vomiting, grade > 1 diarrhea, malabsorption syndrome, obstruction, or
stomach and/or small bowel resection)
10. Psychiatric disorder that interferes with ability to understand the study and give informed
consent, and/or would impact study participation or follow-up
11. Concurrent use of medications that have a relative risk of prolonging the QT interval or of
inducing Torsade de Pointes, if such treatment cannot be discontinued or switched to a
different medication prior to the first dose of study drug
12. 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. WOCBP are defined as sexually
mature women who have not undergone a hysterectomy or surgical sterilizat

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 complete remission rate (CRR, defined as CR or CRi);Secondary Objective: • to assess partial response<br>• to assess time to and duration of remission<br>• to assess event-free and overall survival<br>• to assess safety and tolerability;Primary end point(s): • Complete remission rate (CRR), defined as the number of CR/CRi in patients with<br>refractory de novo AML (Stratum A) or refractory secondary AML (Stratum B). CR and<br>CRi will be assessed by the Investigator according to the response criteria for AML<br>(Cheson, et al 2003) as implemented in the Post-test supplement 1.