Efficacy and Safety of LBH589B in Adult Patients With Multiple Myeloma

Stopped early · Phase 2

Conditions studied: Multiple Myeloma

In brief

This study will evaluate the efficacy and safety of LBH589B in adult patients with multiple myeloma who have received at least two prior therapies and are refractory to their last therapy. Patients must have received in prior therapy either bortezomib or lenalidomide

Key facts

Study ID

NCT00445068

Run by

Novartis Pharmaceuticals

People needed

38

Starts

2007-04-16

Expected to finish

2009-12-25

Last updated by the study team

2021-07-14

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Adults ≥ 18 years old
• 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.
• Patients must have had a diagnosis of symptomatic multiple myeloma (from IMWG see (Kyle et al,2003) meeting all three of the following criteria:
• Monoclonal immunoglobulin (spike on electrophoresis, or band on immunofixation) on serum or on 24 hour urine.
• Bone marrow (clonal) plasma cells or plasmacytoma
• Related organ or tissue impairment (anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity or recurrent infections) (The Kyle et al 2003 definition of symptomatic Myeloma has been adapted based on the new exclusion criteria defined in protocol amendment 1)
• 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 - 100 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 Sixty days is counted from the point in time when the first response assessment is performed after completion of the last line of therapy. At a maximum, disease progression should be documented within 100 days after the last day of the last dose of any anti-MM therapy, including if last regimen of the most recent line of therapy was Autologous Stem Cell Transplant (ASCT). Stable disease patients also part of the IMWG definition are not eligible for this trial. At study screening, Progressive Disease (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 Minimal Response(MR) / Partial Response (PR) / Complete Response (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 bone marrow 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).
• Subjects must have previously been treated with bortezomib and at least one of the following: lenalidomide or thalidomide
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
• Patients must have the following hematological laboratory values:
• Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L (or ≥1.0 x 109/L if the neutropenia is clinically related to progressive myeloma with bone marrow infiltration of > 50% involvement
• Hemoglobin ≥ 8.0 g/dl
• Platelets ≥ 75.0 x 109/L (or ≥ 50.0 x 109/L x if the thrombocytopenia is clinically related to progressive myeloma with bone marrow infiltration > 50% involvement
• Patients must have the following renal function as shown by :
• Calculated Creatinine Clearance (CrCL) > 30ml/min (Cockcroft and Gault formula)
• Patients must have adequate liver function as shown by:
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 2.5 x Upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 x ULN

You may not qualify if…

• Prior therapy with an Histone Deacetylase (HDAC) inhibitor for the treatment of Multiple Myeloma (MM)
• Patients with non-secretory MM
• Patients who have received allogenic stem cell transplantation < 12 months prior to study
• Patients who have had prior allogenic stem cell transplantation and show evidence of active graft versus-host disease that requires immunosuppressive therapy
• Patients with amyloidosis
• Patients with peripheral neuropathy > grade 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 Heart Rate (HR)< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
• Screening Electrocardiogram (ECG) with a corrected QT interval (QTc) > 450 msec
• Right bundle branch block + left anterior hemi-block (bi-fascicular block)
• Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
• Other clinically significant heart disease (e.g., Congestive Heart Failure (CHF NY) Heart Association class III or IV, uncontrolled hypertension, or history of poor compliance with an antihypertensive regimen)
• Impairment of GI function or GI disease that may significantly alter the absorption of LBH589
• Patients with unresolved diarrhea > CTCAE grade 1.
• Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol
• Patients using medications 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
• Concomitant use of CYP3A4 inhibitors
• Patients with an active bleeding diathesis or on any treatment with therapeutic doses of sodium warfarin (Coumadin®) or any other anti-vitamin K drug. Low doses of Coumadin® (e.g., ≤ 2 mg/day), or low doses of any other anti-vitamin K drug, for line patency is allowable
• 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
• Patients who have received high-dose corticosteroids as the only component of their most recent line of therapy
• 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 < 20 mg of prednisone or equivalent as indicated for other medical conditions (and not as maintenance or an anticancer therapy for MM), or up to 100 mg of hydrocortisone as premedication for a administration of certain medications or blood products, while enrolled in this study.
• Patients whose clinical condition would need valproic acid therapy during study or ≤ 5 days prior to starting drug

Where it is running

• Aptium Oncology — Berkeley, California, United States
• City of Hope — Duarte, California, United States
• UCSF — San Francisco, California, United States
• Stanford — Stanford, California, United States
• Rocky Mountain Cancer Center — Denver, Colorado, United States
• Christiana Care — Newark, Delaware, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Emory University — Atlanta, Georgia, United States
• Rush University — Chicago, Illinois, United States
• University of Chicago — Chicago, Illinois, United States
• Mayo Clinic — Scottsdale, Arizona, United States
• Indiana University — Indianapolis, Indiana, United States
• University of Iowa — Iowa City, Iowa, United States
• Dana Farber — Boston, Massachusetts, United States
• University of Michigan — Ann Arbor, Michigan, United States
• Washington University — St Louis, Missouri, United States
• Hackensack University — Hackensack, New Jersey, United States
• Duke — Durham, North Carolina, United States
• Wake Forest — Winston-Salem, North Carolina, United States
• Metrohealth — Cleveland, Ohio, United States
• Sarah Canon Research Center — Nashville, Tennessee, United States
• Vanderbilt — Nashville, Tennessee, United States
• University of Texas Southwestern — Dallas, Texas, United States
• CTRC — San Antonio, Texas, United States
• Novartis investigative Site — Berlin, Germany

Full record on ClinicalTrials.gov

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