Clinical trial NCT02204553: Expanded Treatment Prot of Panobinostat in Combo w/ Bortez and Dex in Pts w/ Relapsed and/or Refractory Multiple Myeloma
Official title: An Expanded Treatment Protocol of Panobinostat (LBH589) in Combination With Bortezomib and Dexamethasone in Patients With Multiple Myeloma Who Have Had at Least One Prior Line of Therapy
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Panobinostat
LBH589
Expanded Access
EAP, ETP
Expanded Treatment
Bortezomib
HDAC
histone deacetylace inhibitor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-07-30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: This will be a multi-center, open label, expanded treatment protocol of panobinostat, bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Panobinostat will be administered at a starting dose of 20mg orally three times a week (every other day) for two weeks on and one week off, with dose adjustments permitted based on observed toxicity. Bortezomib will be administered either intravenously or sub-cutaneously, twice a week on days 1 and 4, two weeks on 1 week off. After 8 cycles of treatment, patients who have achieved stable disease or better by modified EBMT 1998 criteria may continue combination therapy with bortezomib dosing changed to days 1 and 8 of a 21 day cycle for up to 48 weeks of therapy. At the end of the treatment period, (48 weeks) patients with stable disease or better may continue on therapy at the discretion of their investigator until September 2015 or until drug is commercially available, whichever comes first. Patients who have not achieved at least stable disease by 8 cycles must discontinue from study treatment. Dexamethasone will be administered on the day of and the day immediately following bortezomib treatment. Patients will not receive any study treatment during the third week of each cycle. Cycles will be defined as 21 days of treatment. Investigators may not add any other anti-myeloma agents (with the exception of bisphosphonates) while patients remain on study treatment. Patients will remain on study until disease progression, unacceptable toxicity, or end of the study


Eligibility criteria: Inclusion Criteria:

* This study is intended for patients with relapsed and/or refractory multiple myeloma, who have received at least one prior line of therapy. Patients must require retreatment as per IMWG definitions (Kyle et al 2003). Approximately 50-100 patients are expected to be enrolled into this trial.
* Patient has a previous diagnosis of multiple myeloma, based on IMWG 2003 definitions all three of the following criteria had been met:
* Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation on serum or on total 24 hour urine (or demonstration of M protein in cytoplasm of plasma cell for non secretory myeloma).
* 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)
* Patients who have received allogeneic stem cell transplant and do not have active graft vs host disease requiring immunosuppressive therapy are eligible.
* Patient with multiple myeloma (per IMWG 2003 definition) that is relapsed and/or refractory to at least one prior line of therapy and requires retreatment
* Relapsed-and-refractory to a therapy, provided that the patient meets any of the following conditions:
* Relapsed, defined by disease that recurred in a patient that responded under a prior therapy, by reaching a MR or better, and had not progressed under this therapy nor up to 60 days of last dose of this therapy. Patients who previously responded to treatment with BTZ are eligible.
* Patient has relapsed to at least one prior line and patient was refractory to at least one prior line by either not reaching a MR, or progressed while under this therapy, or within 60 days of its last dose. Patients previously refractory to BTZ are also eligible.
* Patients with primary refractory disease are eligible.
* Patients who have previously received high dose therapy/autologous stem cell transplant are eligible
* Patients who have received allogeneic stem cell transplant and do not have active graft vs host disease requiring immunosuppressive therapy are eligible

Exclusion Criteria:

* Patient has shown intolerance to bortezomib, dexamethasone or panobinostat or has any contraindications to any of these therapies. following available prescribing information
* Allogeneic stem cell transplant recipient presenting with graft versus host disease either active or requiring immunosuppression
* Patient has grade ≥ 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination within 14 days of treatment
* Patient taking any anti-cancer therapy concomitantly
* Patient has second primary malignancy \< 3 years of first dose of study treatment (except for treated basal or squamous cell carcinoma, or in situ cancer of the cervix)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers Ironwood Cancer
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group Dept of Highlands Oncology Grp
state: Arkansas
city: Anaheim
country: United States
facility: Kaiser Permanente Medical Group Kaiser Permanente-Moanalua M.C
state: California
city: Berkeley
country: United States
facility: Alta Bates Cancer Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles Hematology/Oncology Medical Group
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center Stanford Cancer Institute (2)
state: California
city: Washington
country: United States
facility: George Washington U Medical Center Medical Faculty Associates
state: District of Columbia
city: Boyton Beach
country: United States
facility: University Cancer Institute Univ. Cancer Institute
state: Florida
city: Hollywod
country: United States
facility: Memorial Cancer Institute Memorial Cancer Inst.
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research SC
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine/Winship Cancer Institute Winship Cancer Institute (2)
state: Georgia
city: Topeka
country: United States
facility: Stormont-Vail Cancer Center
state: Kansas
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic Hematology Oncology Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore Sinai Hospital, Baltimore
state: Maryland
city: Battle Creek
country: United States
facility: Bronson Battle Creek Cancer Care Center
state: Michigan
city: Jackson
country: United States
facility: University of Mississippi Medical Center Cancer Institute
state: Mississippi
city: Kansas City
country: United States
facility: Research Medical Center Research Med. Center
state: Missouri
city: Omaha
country: United States
facility: Oncology Hematology West, PC Nebraska Cancer Specialists
state: Nebraska
city: Little Silver
country: United States
facility: Hematology Oncology of Central New Jersey
state: New Jersey
city: New York
country: United States
facility: Morton Coleman, MD M. Coleman, MD (2)
state: New York
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas GHS Cancer Institute
state: South Carolina
city: Bristol
country: United States
facility: Wellmont Medical Associates
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Arlington
state: Texas
city: Dallas
country: United States
facility: Texas Oncology TX Oncology Baylor
state: Texas
city: Ogden
country: United States
facility: Northern Utah Cancer Associates SC
state: Utah
city: Norfolk
country: United States
facility: Virginia Oncology Associates Virginia Oncology Assoc. (2)
state: Virginia
city: Appleton
country: United States
facility: Fox Valley Hematology and Oncology
state: Wisconsin
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: