A phase Ib/IIb, open-label, multi-center study of oral Panobinostat (LBH589) administered with 5-Azacitidine (Vidaza®) in adult patients with myelodysplastic syndromes (MDS), chronic myelomonocyticleukemia (CMML) or acute myeloid leukemia (AML) - N/A
- Conditions
- Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML)MedDRA version: 14.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10009018Term: Chronic myelomonocytic leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-010548-32-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 64
• Adult patients (age = 18 years) who are candidates for treatment with 5-Aza and present with one of the following:
• intermediate-2 or high-risk myelodysplastic syndromes according to the International Prognostic Scoring System (IPSS). OR
• AML with multilineage dysplasia and maximum of 30% blasts (former RAEB-T according to FAB) OR
• chronic myelomonocytic leukemia (CMML)
• ECOG performance status = 2
• Patients must have the following laboratory values unless elevations are considered due to MDS or leukemia: AST/SGOT and/or ALT/SGPT = 2.5 x ULN; serum creatinine = 1.5 x ULN; serum bilirubin (total and direct) = 2 x ULN; electrolyte panel within normal ranges (WNL) for the institution.
• Negative pregnancy test
• Clinically euthyroid (hypothyroidism corrected with supplementation is permitted).
• 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
• Planned hematopoietic stem-cell transplantation (HSCT)
• Patients with therapy-related MDS
• Patients with therapy-related AML and/or relapsed/refractory AML
• Clinical symptoms suggesting CNS leukemia
• Concurrent therapy with any other investigational agent
• Prior treatment with deacetylase inhibitor(s)
• Prior treatment with 5-Azacytidine or 5-aza-2'-deoxycytidine
• Time windows for prior therapies: Last dose of therapy, including cytokines and/or retinoids, immunotherapy, low-dose ara-C, investigational agent less than 28 days with the exception of hydroxyurea (24 hours) prior to receipt of study medication or AEs that have not recovered at least to NCI CTCAE Grade 1.
• 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 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
• Screening LVEF <45% by echocardiography or MUGA
• Other clinically significant heart disease (e.g. uncontrolled hypertension or history of poor compliance with an antihypertensive regimen).
• Drugs which may cause QT prolongation and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
• Any of concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study. For example:
• 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).
• HIV, Hepatitis B/C infection according to the medical history (testing will not be performed).
• 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 WOCBP 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.
• Suspected hypersensitivity to 5-Aza or Mannitol
• Inability to swallow capsules
• Unwilling or unable to comply with the protocol
• Patient has evidence of clinically significant mucosal or internal bleeding
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: As of amendment 2, primary objective of the phase Ib has been met. The primary objective of the Phase IIb part is to assess preliminary efficacy of treatment with the panobinostat and 5-Aza combination at RPIID relative to treatment with single agent 5-Aza through the assessment of composite CR (CR or CRi or bone marrow CR).;Secondary Objective: •To assess preliminary efficacy of treatment with the panobinostat and 5-Aza combination at RPIID relative to treatment with single agent 5-Aza through the assessment of clinical response other than the composite CR specified in the primary objective, 1-year survival, and time to progression (TTP). <br>•To characterize the safety and tolerability of panobinostat at RPIID in combination with 5-AZA, as well as, 5-AZA alone in the target patient population.<br>;Primary end point(s): As of amendment 2, primary endpoint is Composite CR (CR or CRi or bone marrow CR);Timepoint(s) of evaluation of this end point: Every 8 weeks and at end of trial
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Clinical response for AML: PR; for MDS/CMML: PR and Hematologic Improvement (HI)<br>•Overall response (CR or CRi or bone marrow CR or PR)<br>•1-year survival<br>•Time to progression (TTP) based on the Guidelines for Implementation of IWG response criteria in AML, MDS and CMML according to Cheson 2003 and 2006 Post-text supplement 1 <br>•Type, duration, frequency and relatedness of Adverse Events (AE). AE severity will be assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0)<br>•Laboratory (biochemistry, hematology)<br>•ECG monitoring (central review by eRT)<br>;Timepoint(s) of evaluation of this end point: As per visit schedules