myelodysplastic syndrome MedDRA version: 14.0 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed and dated written informed consent by the patient prior to performance of any study-specific procedures or assessments. 2. Patients of either gender and age =18 years 3. De novo (not therapy-related) MDS LOW or INT-1 according to IPSS 4. Red blood cell transfusion dependency of at least 4 Units within the last 8 weeks before visit 2 (Baseline). Only RBC transfusions given for a Hgb 9.0g/dL, if clinically indicated (e.g. coronary heart disease, long distance travel), respectively, will count 5. Either refractory to ESA or displaying a low chance of response 6. No disease-specific treatment (e.g. Revlimid, Vidaza) within 4 weeks prior to visit 2 (Baseline). Treatment for transfusional iron overload with EMEA approved drugs is allowed) 7. Age-adjusted normal cardiac, kidney, liver function (creatinine =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known hypersensitivity to study drugs or their compounds 2. Concomitant use of ESA 3. Concomitant use of any other investigational drug 4. Other malignancy that is not in remission for least 1 year 5. HIV or other uncontrolled infection 6. Any peripheral neuropathy = CTCAE grade 2 7. Unresolved diarrhea = CTCAE grade 2 8. Platelet Count 100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet other exclusion criteria • Clinically significant resting bradycardia ( 470 msecs on screening ECG • Right bundle branch block + left anterior hemiblock (bifasicular block) • Angina pectoris = 3 months prior to starting study drug • Acute myocardial infarction = 3 months prior to starting study drug • Other clinically significant heart disease (e.g., CHF, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) • History (within previous 6 months prior to starting study drug) of deep venous thrombosis (DVT) or cerebrovascular accident (CVA) 10. Impairment of GI function or GI disease that may significantly alter the absorption of LBH589 (e.g. acute or chronic ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) 11. Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection, uncontrolled chronic obstructive or chronic restrictive pulmonary disease) that could cause unacceptable safety risks or compromise compliance with the protocol 12. History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative 13. History of drug or alcohol abuse within the 12 months prior to starting study drug 14. Pregnancy or breast feeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the hematological improvement of the erythropoietic system (HI-E) using modified IWG criteria in patients treated for 4 months with LBH589 single agent. ;Secondary Objective: • To compare the hematological improvement of the erythropoietic system (HI-E) using modified IWG criteria in patients treated for 8 to 12 months with either LBH589 single agent or with LBH589 and ESA combination treatment. • To evaluate the objective response rate at 4, 8 and 12 months of treatment according to modified IWG criteria • To determine the IPSS status as well as the single scoring values of the IPSS for patients at baseline and EOS. • To determine time to response, event-free survival, progression-free survival, disease-free survival, time to cause-specific death, and overall survival in this patient population. • To evaluate the safety and tolerability profile of LBH589 and LBH589 + ESA in low and INT-1 risk MDS patients treated for up to 12 months. • To evaluate the hematological improvement of the erythropoietic system using modified IWG criteria in patients treated for 4 months with LBH589 and ESA combination treatment.;Primary end point(s): The primary efficacy variable of this study will be the rate of patients showing an improvement of the erythropoietic system (HI-E) after four months according to the modified IWG criteria. If the response is lost during the timeframe of two months after its initial observation (or premature discontinuation), this will not be accounted for as an improvement for the primary analysis. | — |
Countries
Germany
Outcome results
None listed