A Phase II study of single agent oral panobinostat in patients with refractory de novo or secondary acute myelogenous leukemia (AML) - ND
- Conditions
- adult patients with refractory de novo or secondary acute myelogenus leukemia (AML)MedDRA version: 12.0Level: LLTClassification code 10000886Term: Acute myeloid leukemia
- Registration Number
- EUCTR2008-002983-32-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
Stratum A Specific Inclusion Criterion: Refractory AML with confirmed initial diagnosis of de novo AML (excludes APL)
Stratum B Specific Inclusion Criterion: Refractory AML with confirmed initial diagnosis of AML (excludes 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), other therapies (e.g. lenalidomide) 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 defined 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 calcium (corrected for serum 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 (NCI CTCAE Gr 1) unless attributed to underlying disease 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 initial 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 chemotherapy, including ≤ Gr 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
1.Patients with initial diagnosis of AML secondary to ionizing radiation/cytotoxic therapy (e.g. alkylating agents) for precedent 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 graft versus host (GVH) directed therapy 5.Patients who have received either hydroxyurea or glucocortico-steroids for prevention of leukostasis less than 24 hrs before the first dose of study drug 6.Patients with another malignancy (with the exception of prior MDS for secondary AML patients in Stratum B) unless disease-free for at least 3 yrs 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 myocardial infarction (MI) within 6 mos Other clinically significant heart disease (e.g. uncontrolled hypertension or history of poor compliance with a 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 mos following the last dose of study drug. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or surgical sterilization or who have not been postmenopausal for a
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 to assess time to and duration of remission to assess event-free and overall survival to assess safety and tolerability;Primary end point(s): complete remission rate (CRR), defined as CR/CRi (Cheson, et al 2003) as implemented in the Post-text Supplement 1 in each of the two strata.
- Secondary Outcome Measures
Name Time Method