Safety Study of LBH589 When Given in Combination With Bortezomib in Adult Patients With Multiple Myeloma

Completed · Phase 1

Conditions studied: Multiple Myeloma

In brief

This study comprises of a dose-escalation and dose expansion phase and will determine the maximum tolerated dose of oral Panobinostat on a continuous schedule in adult in combination with bortezomib. Safety, tolerability, PK and PD profile of the combined treatments will be assessed as secondary objectives. Dose expansion phase will explore in a non continuous Panobinostat schedule with bortezomib and dexamethasone, safety and tolerability and PK profile of Panobinostat and Bortezomib with and without Dexamethasone

Key facts

Study ID

NCT00532389

Run by

Novartis Pharmaceuticals

People needed

62

Starts

2007-10-01

Expected to finish

2013-10-01

Last updated by the study team

2020-12-19

Who can join

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

You may qualify if…

• 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.
• Patients must have received at least one prior line of therapy and includes patients whose disease has relapsed as well as relapsed-refractory MM . (Durie et. al., 2006). One prior line of therapy may consist of induction followed by autologous stem cell transplantation.
• Patients must be suitable (according to their local product information and applicable health authority recommendations) for treatment with BTZ. Note: patients previously treated with BTZ are eligible to participate in the trial.
• Patients enrolled to dose expansion phase must have measurable M component at entry according to the IMWG Criteria (Durie et al, 2006) including at least one of the following:
• Serum M-protein by sPEP ≥ 1 g/dL (> 10g/l)
• For patients with IgA M-protein whose sPEP is not providing sufficiently precise quantification due to confounded migration of M-protein with serum beta globulins, a quantification by nephelometry / turbidometry is permitted and must show serum M-protein ≥ 1 g/dL
• Urine M-protein by uPEP ≥ 200 mg/24 h
• Serum FLC assay: Involved FLC level ≥ 100 mg/L, provided serum FLC ratio is abnormal. (abnormal if FLC ratio is <0.26 or >1.65 )
• Adults ≥ 18 years old
• ECOG Performance Status ≤ 2
• Life expectancy > 12 weeks
• Patients must have the following laboratory values:
• ANC ≥ 1.5 x 109/L
• Platelets ≥ 100x 109/L
• Calculated CrCl ≥ 30 mL/min (MDRD Formula)
• AST and ALT ≤ 2.5 x ULN
• Serum bilirubin ≤ 1.5 x ULN
• Serum potassium, magnesium, phosphorous, within normal limits (WNL) for institution
• Total calcium (corrected for serum albumin) or ionized calcium equal to lower normal limits for institution or greater (≥ LLN) but not higher than CTCAE grade 1
• Note: Potassium, calcium, magnesium, and/or phosphorous supplements may be given to correct values that are < LLN.
• Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal
• All patients (dose-escalation and dose-expansion patients) must be willing to undergo a mandatory bone marrow aspirate sampling at baseline (for cytology) and another later in the study if the patient eventually goes on to experience a CR or PR. For patients who join the study at the dose-expansion phase, they must also give consent to have an extra volume of sample taken for exploratory biomarker testing. Potential dose-expansion phase patients who do not consent for this biomarker sample collection will not be eligible to participate in the trial (Note: One extra bone aspirate sample at C2D1 is optional as per the protocol).
• Able to sign informed consent and to comply with the protocol
• Patient is able to swallow capsules

You may not qualify if…

• Prior exposure to a HDAC inhibitor compound used in the treatment of MM
• Patients with Refractory MM (i.e. patients refractory to all prior therapies) who under all prior previous lines of therapy have :
• either never reached a response better than SD
• or whose disease progressed from any best response while still under therapy
• or whose disease progressed within 60 days of last dose of therapy
• Patients who have had prior allogeneic stem cell transplantation and show evidence of active graft-versus-host disease or of graft-versus-host disease that requires immunosuppressive therapy.
• Patient has grade 1 peripheral neuropathy with pain or grade ≥ 2 peripheral neuropathy on clinical examination within 14 days before first study treatment
• 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)
• Impairment of GI function or GI disease that may significantly alter the absorption of PAN
• Patient has unresolved diarrhea ≥ CTCAE grade 2
• Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infection, acute diffuse pulmonary disease, pericardial disease, uncontrolled thyroid dysfunction ) including abnormal laboratory values, 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 torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
• Patients who need valproic acid for any medical condition during the study or within 5 days prior to the first PAN treatment.
• 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.
• Patients who have received either immunotherapy within ≤ 8 weeks; chemotherapy within ≤ 4 weeks; or radiation therapy to > 30% of marrow-bearing bone within ≤ 2 weeks prior to starting study treatment; or who have not yet recovered from side effects of such therapies.
• Patients who have received steroids (e.g. Dex) ≤ 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.
• Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy

Where it is running

• Innovative Medical Research of South Florida Dept.ofInnovativeMedResearch — Miami Shores, Florida, United States
• Dana Farber Cancer Institute Clinical Research Coordinator — Boston, Massachusetts, United States
• Hackensack University Medical Center Multiple Myeloma Division — Hackensack, New Jersey, United States
• Swedish Medical Center Dept.ofSwedishMedicalCtr. — Seattle, Washington, United States
• Novartis Investigative Site — Canberra, Australian Capital Territory, Australia
• Novartis Investigative Site — Vancouver, British Columbia, Canada
• Novartis Investigative Site — Montreal, Quebec, Canada
• Novartis Investigative Site — Berlin, Germany
• Novartis Investigative Site — Kiel, Germany
• Novartis Investigative Site — Leipzig, Germany
• Novartis Investigative Site — München, Germany
• Novartis Investigative Site — Würzburg, Germany
• Novartis Investigative Site — Bologna, BO, Italy
• Novartis Investigative Site — Torino, TO, Italy
• Novartis Investigative Site — Salamanca, Castille and León, Spain
• Novartis Investigative Site — Barcelona, Catalonia, Spain

Full record on ClinicalTrials.gov

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