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

• Conditions: MedDRA version: 8.1Level: LLTClassification code 10028228Term: Multiple myeloma; Patients with relapsed multiple myeloma who have received at least two prior lines of therapy and whose disease is refractory to the most recent line of therapy. Prior therapy must have included bortezomib or lenalidomide.

• Registration Number: EUCTR2006-004087-31-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-26
• Last Update Posted: 7 January 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

1. Adults = 18 years old
2. Subjects must have signed the consent form before undergoing any study specific screening procedures and before participation in this study. The subject must be fully informed by the investigator of the nature and potential risks of participation in this study.
3. Diagnosis of symptomatic multiple myeloma. All three of the following criteria must be met:
• Monoclonal immunoglobulin (spike on electrophoresis, or band on immunofixation) on serum or on 24 hour urine (or demonstration of M protein in cytoplasm of plasma cell for non secretory myeloma) .
• Bone marrow (clonal) plasma cells or plasmacytoma
• Related organ or tissue impairment (anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections)
4. Subjects must have received at least two prior lines of therapy and be refractory to the most recent line of therapy according to the following definitions:

Refractory to most recent line of therapy
• Defined by disease progression during treatment or within 60 days after the completion of the most recent line of therapy. This includes the development of disease progression during maintenance or consolidation therapy with high dose glucocorticoids, or any other specific MM therapy
• At study screening, PD will be assessed by comparing screening values or symptoms in reference to the baseline (values or symptoms) of their last line of therapy . Should a patient have experienced an initial response on their last line of therapy, PD should be assessed in reference to the lowest values of the initial confirmed response (MR/PR/CR)

Disease progression is defined by having one or more of the following:
• >25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation.
• >25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200 mg/24 h and confirmed on a repeat investigation.
• >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%.
• Definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas.
• Development of new bone lesions or soft tissue plasmacytomas (not including compression fracture).
• Development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).

5. Subjects must have previously been treated with bortezomib or lenalidomide
6. ECOG PS = 2
7. All baseline studies must be performed within 21 days prior to first dose of LBH589
8. Patients must have special hematological laboratory values (details see study protocol)
9. Patients must have adequate renal function (details see study protocol)
10. Patients must have adequate liver function (details see study protocol)
11. Patients must have special non-hematological laboratory values (details see study protol)
12. Baseline MUGA or ECHO must demonstrate LVEF = the lower limit of the institutional normal
13. Patients must be willing and able to undergo bone marrow aspirates as per protocol, with/without bone marrow biopsy according to their center’s practice. The bone marrow aspirate/biopsy must be adequate to allow for comparison for the later efficacy response assessments.
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

Exclusion Criteria

1. Prior therapy with an HDAC inhibitor
2. 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
3. Other clinically significant heart disease (e.g., CHF NYHA class III or IV , uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
4. Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
5. Patients with unresolved diarrhea > CTCAE grade 1
6. Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
7. Patients using medications listed in Post-text supplement 1 that have a relative risk of prolonging the QT interval or inducing torsades de pointes if the medications cannot be discontinued or switched to a different medication prior to starting study drug
8. Concomitant use of CYP3A4 inhibitors (see Post-text supplement 1)
9. Patients with an active bleeding diathesis or on any treatment with therapeutic doses of sodium warfarin or any other anti-vitamin K drug. Low doses of sodium warfarin (e.g., = 2 mg/day), or low doses of any other anti-vitamin K drug, for line patency is allowable
10. Patients who have received chemotherapy, radiation therapy or any investigational drugs, bortezomib or other immunomodulatory therapy (e.g., thalidomide, lenalidomide) or immunotherapy = 3 weeks prior to starting study drug or who have not recovered from side effects of such therapy
11. 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 subjects 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.
12. Patients who have received high-dose corticosteroids as the only component of their most recent line of therapy
13. Patients who have undergone major surgery = 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
14. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of oral LBH589
15. Male patients whose sexual partners are WOCBP not us

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified