Clinical trial NCT00773838: Study of Vorinostat (MK0683), an Histone Deacetylase (HDAC) Inhibitor in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (MK-0683-095)
Official title: An International, Multicenter, Open-Label Study of Vorinostat (MK0683) in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed or Refractory Multiple Myeloma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-10-16
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the clinical activity of vorinostat in combination with bortezomib in participants with relapsed or refractory multiple myeloma after at least 2 prior treatment regimens. The primary objective is to define the objective response rate (RR) associated with the administration of vorinostat in combination with bortezomib to patients with relapsed and refractory multiple myeloma after at least 2 prior treatment regimens. The primary hypothesis of the study is the administration of vorinostat in combination with bortezomib will result in a clinically meaningful rate of objective response.

Detailed description: The protocol has been amended to indicate that the Final Analysis is designated as the time when the primary endpoint of 29 responders has been met, or the time when all participants have discontinued treatment or have been enrolled in the study for at least 6 months (if the primary endpoint is not reached by this time). Following the Final Analysis, participants will be allowed to continue study treatment in an extension as long as they have not met the criteria for discontinuation, and will be followed for overall survival and serious AEs.

Eligibility criteria: Inclusion Criteria:

* Has an established diagnosis of multiple myeloma based on myeloma diagnostic criteria
* Must have adequate organ function
* Is refractory to prior bortezomib regimen and have also been exposed to prior Immunomodulatory imide drugs (IMiD: thalidimide or lenalidmide)
* Has relapsed and refractory multiple myeloma after at least 2 prior treatment regimens
* Has performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
* Has measurable disease, defined as any quantifiable serum monoclonal (M) protein value and, where applicable, urine light chain of ≥200 mg/24 hours
* Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 30 days after the last dose of study intervention
* Male participants must agree to use approved contraception during the treatment period and for at least 30 days after the last dose of study intervention and refrain from donating sperm during this period
* Is relapsed, refractory, intolerant, and/or ineligible (in the opinion of the investigator) to other therapies including an IMiD (thalidomide or lenalidomide)
* Is refractory to bortezomib (no response on prior bortezomib containing regimen or progression on or within 60 days of bortezomib containing regimen

Exclusion Criteria:

* Has known hypersensitivity to any components of bortezomib or vorinostat
* Has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone marrow transplantation within 4 weeks of the initiation of study therapy
* Has an active systemic infection
* Has acute diffuse infiltrative pulmonary disease or pericardial disease
* Has known hypersensitivity to any components of bortezomib or vorinostat
* Has active Hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus (HIV) positive
* Has history of a prior malignancy with the exception of cervical intraepithelial neoplasia; non-melanoma skin cancer; adequately treated localized prostate carcinoma with prostate specific antigen (PSA) \< 0.1; or who has undergone potentially curative therapy with no evidence of that disease for five years, or who is deemed at low risk for recurrence by his/her treating physician
* Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has plasma cell leukemia defined as the presence of more than 20% plasma cells in the peripheral blood and an absolute plasma cell count of at least 2000/μL
* Has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug
* Has preexisting National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Grade 1 neuropathy with pain or \>Grade 2 neuropathy

Primary outcomes:
measure: Objective Response Rate (RR)
timeFrame: Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)
Secondary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 22 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 18 months
measure: Time To Disease Progression (TTP) as Determined by IAC Per EBMT Criteria
timeFrame: Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)
measure: TTP as Assessed by Investigator Per EBMT Criteria
timeFrame: Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)
measure: Progression-Free Survival (PFS) as Determined by IAC Per EBMT Criteria
timeFrame: Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)
measure: PFS as Assessed by Investigator Per EBMT Criteria
timeFrame: Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)
measure: Overall Survival (OS)
timeFrame: Up to approximately 40 months (through End of Trial data cut-off of 09-Apr-2012)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Siegel DS, Dimopoulos M, Jagannath S, Goldschmidt H, Durrant S, Kaufman JL, Leleu X, Nagler A, Offner F, Graef T, Eid JE, Houp J, Gause C, Vuocolo S, Anderson KC. VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2016 Jun;16(6):329-334.e1. doi: 10.1016/j.clml.2016.02.042. Epub 2016 Mar 4.