multiple myeloma MedDRA version: 9.1 Level: LLT Classification code 10028228 Term: Multiple myeloma
Conditions
Interventions
Product Name: PANOBINOSTAT
Product Code: LBH589
Pharmaceutical Form: Capsule, hard
CAS Number: 404950-80-7
Current Sponsor code: LBH589
Concentration unit: mg milligram(s)
Concentration type: equal
Co
Sponsors
NOVARTIS FARMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have a diagnosis of active multiple myeloma according to the International Myeloma Working Group criteria (IMWG et.al., 2003), and be deemed by the investigator as requiring treatment. 2. Patients must have received at least one prior line of therapy and their disease has relapsed (Durie et. al., 2006). One prior line of therapy may consist of induction followed by autologous stem cell transplantation. 3. Patients must be suitable (according to their local product information) for treatment with bortezomib. Note: patients previously treated with bortezomib are eligible to participate in the trial. 4. Adults ≥ 18 years old 5. ECOG Performance Status ≤ 2 6. Life expectancy > 12 weeks 7. Patients must have the following laboratory values: ANC ≥ 1.5 x 109/L Hemoglobin ≥ 9 g/dl Platelets ≥ 100x 109/L Calculated CrCl ≥ 50 mL/min (MDRD Formula) AST and ALT ≤ 2.5 x ULN Serum bilirubin ≤ 1.5 x ULN Albumin > 3.0 g/dl Serum potassium ≥ LLN Total serum calcium [corrected for serum albumin] or ionized calcium ≥LLN, Serum magnesium ≥ LLN Serum phosphorus ≥ LLN TSH ≤ LLN and free T4 within normal limits. Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism. Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal Patients participating in the dose-expansion phase of the trial must be willing and able to undergo bone marrow aspirates as per protocol, with/without bone marrow biopsy according to their center?s practice Able to sign informed consent and to comply with the protocol 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
Exclusion criteria: 1. Prior exposure to a HDAC inhibitor compound used in the treatment of MM 2. Primary refractory MM 3. Patients who have received allogeneic stem cell transplantation 450 msec Right bundle branch block + left anterior hemiblock (bifascicular block) Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug Other clinically significant heart disease (e.g., CHF NY Heart Association class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) 7. Impairment of GI function or GI disease that may significantly alter the absorption of LBH589 8. Patients with diarrhea > CTCAE grade 1 9. Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol 10. Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug 11. Concomitant use of CYP3A4 inhibitors 12. Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (which ever is longer) and who have not recovered from side effects of those therapies. 13. Patients who have received either immunotherapy within 30% of marrowbearing bone within < 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies. 14. Patients with an active bleeding tendency or is receiving any treatment with therapeutic doses of sodium warfarin (Coumadin) or coumadin derivatives. Low doses of Coumadin (e.g. ≤ 2 mg/day) to maintain line patency (if applicable) is allowed. 15. Patients who have received steroids (e.g. dexamethasone) ≤ 2 weeks prior to starting study treatment or who have not recovered from side effects of such therapy. Concomitant therapy medications that include corticosteroids are allowed if patients receive < 10 mg of prednisone or equivalent as indicated for other medical conditions, or up to 100 mg of hydrocortisone as pre-medication for administration of certain medications or blood products while enrolled in this study. 16. Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy 17. Women who are pregnant or breast feeding or women of childbearing po
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the MTD of LBH589 and bortezomib when administered in combination;Secondary Objective: To characterize the safety and tolerability of the study treatment To characterize the PK profile of bortezomib in combination with LBH589 To compare the PK profile of LBH589 with and without bortezomib To characterize the PD profile of the study treatment through the analysis of various biomarkers To assess the preliminary efficacy of the study treatment;Primary end point(s): Safety: The incidence of dose limiting toxicities (DLT) | — |
Countries
Italy
Outcome results
None listed