A phase Ib, multi-center, open-label, dose-escalation study of oral LBH589 when administered in combination with oral lenalidomide & dexamethasone in adult patients with multiple myeloma
- Conditions
- Multiple MyelomaMedDRA version: 14.1Level: PTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2006-007030-35-IT
- Lead Sponsor
- OVARTIS FARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 40
1. Patients must have a diagnosis of active multiple myeloma according to the International Myeloma Working Group criteria (IMWG, 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 lenalidomide & dexamethasone. Note: patients previously treated with lenalidomide & dexamethasone 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. 8. Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal 9. 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 10. 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: 0
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) no
F.1.3.1 Number of subjects for this age range
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 < 12 months prior to entering the study 4.Patients who have had prior allogeneic stem cell transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy. 5.Peripheral neuropathy > CTCAE grade 2 6.Impaired cardiac function or clinically significant cardiac diseases, including any one of the following: ? Patients with congenital long QT syndrome ? History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the Sponsor prior to enrollment) ? Any history of ventricular fibrillation or torsade de pointes ? Bradycardia defined as HR< 50 bpm.Patients with pacemakers are eligible if HR ≥ 50 bpm. ? Screening ECG with a QTc > 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 with a history of Deep Vein Thrombosis or thromboembolism within < 6 months prior to starting study treatment 13.Patients for whom prophylactic anticoagulation therapy (eg.325mg aspirin PO daily or warfarin (Coumadin) 1-2 mg/day, or any other coumarinderivative anticoagulants) is not an option. 14.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. 15.Patients who have received either immunotherapy within < 8 weeks; chemotherapy within < 4 weeks; or radiation therapy to > 30% of marrowbearing bone within < 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies. 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 potential (WOCBP) who are unable to use two reliable forms of contraception simultaneously, unless continuous abstinence from heterosexual contact is the chosen method.WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months).WOCBP should have 2 negative pregnancy tests
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: To characterize the safety and tolerability of the study treatment ? To characterize the PK profile of LBH589 when it is administered in combination with lenalidomide & dexamethasone, and to evaluate the degree of influence of dexamethasone CYP450 moderate induction on LBH589 trough levels ? To characterize the PD profile of the study treatment through the analysis of various biomarkers in the context of this combination ? To assess the preliminary efficacy of the study treatment;Primary end point(s): To determine the MTD of LBH589 when used in combination with a fixed dose of lenalidomide & dexamethasone.;Main Objective: To determine the MTD of LBH589 when used in combination with a fixed dose of lenalidomide & dexamethasone.
- Secondary Outcome Measures
Name Time Method