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

NCT00532389 | Completed Phase 1

• 2 other identifiers: CLBH589B22072006-006638-16
• Study Type: interventional
• Target: 62
• Locations: 6 countries
• Sites: 16

Brief Summary

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

Conditions

Multiple Myeloma

Keywords

Myeloma; Multiple Myeloma; Bortezomib; LBH589; Combination

Outcome Measures

Primary Outcomes (1)

• To determine the MTD of panobinostat with bortezomib

  throughout the study

Secondary Outcomes (3)

• The safety and tolerability of the study continuous Panobinostat treatment in dose escalation phase and non continuous schedule of panobinostat in dose expansion phase

  throughtout the study

• To characterize the PK profile of bortezomib; the PK profile of panobinostat with and without bortezomib; the PK profile of bortezomib and panobinostat with and without dexamethasone

  cycle 1 & cycle 2

• To assess the preliminary efficacy of the study treatment

  throughout the study

Study Arms (1)

Panobinostat (LBH589)

EXPERIMENTAL

Drug: LBH589

Interventions

LBH589 DRUG

Panobinostat (LBH589)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (16)

Innovative Medical Research of South Florida Dept.ofInnovativeMedResearch

Miami Shores, Florida, 33138, United States

Location

Dana Farber Cancer Institute Clinical Research Coordinator

Boston, Massachusetts, 02115, United States

Location

Hackensack University Medical Center Multiple Myeloma Division

Hackensack, New Jersey, 07601, United States

Location

Swedish Medical Center Dept.ofSwedishMedicalCtr.

Seattle, Washington, United States

Location

Novartis Investigative Site

Canberra, Australian Capital Territory, 2606, Australia

Location

Novartis Investigative Site

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

München, 80336, Germany

Location

Novartis Investigative Site

Würzburg, 97070, Germany

Location

Novartis Investigative Site

Bologna, BO, 40138, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Salamanca, Castille and León, 37007, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Related Links

• Results for CLBH589B2207 can be found on the Novartis Clinical Trial Results Website

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Panobinostat

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2007
• First Posted: September 20, 2007
• Study Start: October 1, 2007
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 19, 2020

Record last verified: 2014-10

Locations

CA (2); AU (1); US (4); DE (5); ES (2); IT (2)