A Phase II Study Of Oral LBH589 In Adult Patients With Multiple Myeloma Who Have Received At Least Two Prior Lines Of Therapy And Whose Disease Is Refractory To The Most Recent Line Of Therapy

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 14

Inclusion Criteria

1. Diagnosis of symptomatic multiple myeloma (from IMWG see (Kyle, et al 2003)). All three of the following criteria must be met:
a). Monoclonal immunoglobulin (spike on electrophoresis, or band on immunofixation) on serum or on 24 hour collected urine (or demonstration of M protein in cytoplasm of plasma cell for non secretory myeloma)
b). Bone marrow (clonal) plasma cells or plasmacytoma
c). Related organ or tissue impairment (anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections)
2. Subjects must have received at least two prior lines of therapy (including either bortezomib or lenalidomide) and be refractory to the most recent line of therapy according to the following definitions:
3. ECOG <= 2
4. Patients must have the following hematological laboratory values:
- ANC >= 1.5 x 109/L
- Hemoglobin >= 8 g/dl
- Platelets >= 75 x 109/L
- 24 -hour measured GFR CrCl >= 50 mL/min, or if not available, by serum creatinine < 2 x ULN)
- AST(SGOT) and ALT (SGPT) <= 2.5 x ULN
- Serum bilirubin <= 1.5 x ULN
- Serum albumin >= 2.5 g/dl
- Serum potassium, phosphorus, calcium and magnesium >= LLN,
- Normal thyroid function (TSH and free T4) (hypothyroidism correctable with supplements is allowed)
5. Baseline MUGA or ECHO must demonstrate LVEF >= the lower limit normal

Exclusion Criteria

1. Prior therapy with an HDAC inhibitor
2. Impaired cardiac function, including: screening ECG with a QTc > 450 msec, congenital long QT syndrome, history or presence of sustained ventricular tachyarrhythmia, ventricular fibrillation or torsades de pointes, bradycardia (< 50 bpm), myocardial infarction or unstable angina <= 6 months prior to starting study drug, congestive heart failure (NYHA class III or IV), right bundle branch block or left anterior hemiblock and uncontrolled hypertension
3. Patients using medications that have a relative risk of prolonging the QT interval or inducing torsades de pointes
4. Concomitant use of CYP3A4 inhibitors
5. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LBH589 (including diarrhea > CTCAE grade 1)
6. Other concurrent severe and/or uncontrolled medical conditions
7. Patients who have received radiation therapy, chemotherapy, any investigational drugs, immunomodulatory therapy or immunotherapy <= 3 weeks prior to starting study drug.
8. Patients who have undergone major surgery <= 4 weeks prior to starting study drug
9. Patients who have received high-dose steroids <= 2 weeks prior to starting study drug
10. Patients who have received high-dose corticosteroids as the only component of their most recent line of therapy

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Hematologic response: measurements as per Bladé criteria, including levels of<br /><br>serum M-protein, serum FreeLite (TM), Bence-Jones protein in urine, bone marrow<br /><br>differential, skeletal survey (on indication) for osteolytic lesions as well as<br /><br>radiological examiniations in case of extramedullar plasmacytomas.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Determination and calculation of disease evaluation per criteria in Bladé<br /><br>(1998) and per Durie (2006) using the parameters as described in the primary<br /><br>parameters.<br /><br>Safety and tolerability will be evaluated using assessments of (serious)<br /><br>adverse events (frequency) and laboratory data (new, worsening or improving<br /><br>values) using the CTCAE Grading scales.</p><br>

Related Trials