Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma

NCT01083602 | Completed Phase 2 Results

• 1 other identifier: CLBH589DUS71
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 13

Brief Summary

This study is designed to assess the effectiveness of the combination of Panobinostat plus Bortezomib and Dexamethasone in patients with relapsed and bortezomib refractory Multiple Myeloma.

Conditions

Relapsed and Bortezomib Refractory Multiple Myeloma; Refractory Multiple Myeloma; Multiple Myeloma in Relapse

Keywords

Multiple Myeloma; Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (PR+nCR+CR)

  Overall response rate=(PR+nCR+CR) CR= \< 5% plasma cells in bone marrow. No confirmation on bone marrow plasma cell (additional assessment) is needed to document CR except patients with non-secretory myeloma where the bone marrow examination must be repeated after an interval of at least 6 weeks, Absence of M-protein in serum and urine by immunofixation,nCR same as CR without out Absence of M-protein in serum and urine by immunofixation,PR+ 50% reduction of serum M-protein and sofft tissue Plasmacytomas all for more than 6 weeks.

  after eight cycyles of treatment (24 weeks)

Secondary Outcomes (5)

• Responders to Treatment

  after eight cycyles of treatment (24 weeks)

• Time to Response (Greater Than or Equal to PR) Based on Investigator Assessment

  after eight cycyles of treatment (24 weeks)

• Progression-free Survival

  24 weeks

• Time to Progression

  24 weeks

• Over All Survival

  24 weeks

Study Arms (1)

panobinostat + bortezomib & dexamethasone

EXPERIMENTAL

panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory multiple myeloma

Drug: panobinostat; Drug: bortezomib; Drug: dexamethasone

Interventions

panobinostat DRUG

PAN 20 mg PO given TIW, weeks 1\&2 of each 3-week cycle;• BTZ 1.3 mg/m2 IV push given BIW weeks 1\&2 of each 3 week cycle (days 1,4,8 and 11);• Dex 20 mg PO given QIW, weeks 1\&2 of each 3-week cycle (days 1,2,4,5,8,9,11 and 12)

Also known as: LBH589, PAN

panobinostat + bortezomib & dexamethasone

bortezomib DRUG

Also known as: BTZ

panobinostat + bortezomib & dexamethasone

dexamethasone DRUG

Also known as: DEX

panobinostat + bortezomib & dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patient has a previous diagnosis of multiple myeloma, based on IMWG 2003 definitions. All three of the following criteria must have been met:
• Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation on serum or on total 24 hour urine
• Bone marrow (clonal) plasma cells ≥ 10% or biopsy proven plasmacytoma
• Related organ or tissue impairment (CRAB symptoms: anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections)
• Patient must have relapsed and refractory MM and must require treatment for the relapsed disease
• Patients must have received at least 2 prior lines of therapy which include an IMiD (thalidomide or lenalidomide)
• Patient must be refractory to the last bortezomib containing line of therapy given in the relapsed and refractory setting defined as:
• having progressed on or within 60 days of the last bortezomib-containing line of therapy
• Patient has measurable disease on M protein at study screening defined by at least one of the following measurements as per thresholds clarified in IMWG 2003 disease definitions (Kyle, et al 2003):
• Serum M-protein ≥ 1 g/dL (≥ 10 g/L)
• Urine M-protein ≥ 200 mg/24 h
• Patients treated with local radiotherapy with or without concomitant exposure to steroids for pain control or management of cord/nerve root compression, are eligible. Two weeks must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and 2 weeks have passed since the last date of therapy
• Patient's age is ≥ 18 years at time of signing the informed consent
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2
• Patient has the following laboratory values within 3 weeks before starting study drug (lab tests may be repeated, as clinically indicated, to obtain acceptable values before screen fail is concluded but supportive therapies are not to be administered within the week prior to screening tests for absolute neutrophil count or platelet counts)

You may not qualify if:

• Primary refractory disease (patients that never reached at least an MR for over 60 days under any prior therapy)
• Patients who have a history of prior MM treatment with a DAC inhibitor including panobinostat
• Patients who have had prior allogeneic stem cell transplantation and show evidence of active graft-versus-host disease that requires immunosuppressive therapy
• Peripheral neuropathy ≥ CTCAE grade 2
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to the first administration of study drug / treatment or who cannot be switch to safely to alternative anti-epileptic medication
• Patients who have impaired cardiac function including any of the following:
• Congenital long QT syndrome, complete left bundle branch block or use of a permanent cardiac pacemaker, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (\< 50 beats per minute). Right bundle branch block + left anterior hemiblock (bifascicular block)
• QTcF \> 450 msec on screening ECG
• Previous history of angina pectoris or acute MI within 6 months
• Congestive heart failure (New York Heart Association functional classification III-IV)
• Patient has any other clinically significant cardiovascular disease (e.g. uncontrolled hypertension)
• Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or significant small bowel resection)
• Patient has unresolved diarrhea ≥ CTCAE grade 2
• Patients who have any other concurrent severe and/or uncontrolled medical condition(s) including, but not limited to: uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease (e.g. dyspnea at rest from any cause), symptomatic thyroid dysfunction, significant bleeding tendency, that could cause unacceptable safety risks or compromise compliance with the protocol
• Patients who are using medications that have a known relative risk of prolonging the QT interval or of inducing Torsade de Pointes, where such treatment cannot be discontinued or switched to a different medication prior to starting study drug

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center Division of Hematology

Stanford, California, 94305-5826, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Emory University School of Medicine/Winship Cancer Institute Dept. of Winship Cancer Inst.

Atlanta, Georgia, 30322, United States

Location

Georgia Regents University MedCollege of GA Cancer Ctr 2

Augusta, Georgia, 30912, United States

Location

Hematology/Oncology of the North Shore Orchard Healthcare Res. Inc.

Skokie, Illinois, 60076, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Somerset Hematology Oncology Associates Somerset Hema Oncol Assoc (2)

Somerset, New Jersey, 08873, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Duke University Medical Center Dept. of DUMC (4)

Durham, North Carolina, 27710, United States

Location

Vanderbilt University Medical Center, Clinical Trials Center Vanderbilt UMC

Nashville, Tennessee, 37212, United States

Location

MD Anderson Cancer Center/University of Texas MD Anderson CC

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Richardson PG, Schlossman RL, Alsina M, Weber DM, Coutre SE, Gasparetto C, Mukhopadhyay S, Ondovik MS, Khan M, Paley CS, Lonial S. PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma. Blood. 2013 Oct 3;122(14):2331-7. doi: 10.1182/blood-2013-01-481325. Epub 2013 Aug 15.

  PMID: 23950178 DERIVED

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Panobinostat; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; 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; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Steven Young, M.D.

  Somerset Hematology Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2010
• First Posted: March 10, 2010
• Study Start: June 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: December 21, 2017
• Results First Posted: March 27, 2015

Record last verified: 2017-11

Locations

US (13)