Study of Vorinostat (MK0683), an Histone Deacetylase (HDAC) Inhibitor in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma (MK-0683-095)

NCT00773838 | Completed Phase 2 Results DMC

• 4 other identifiers: 0683-0952008-003753-33MK-0683-0952008_524
• Study Type: interventional
• Target: 143
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (RR)

  Objective RR was defined as percentage (%) of participants with complete response (CR: disappearance of original monoclonal (M) paraprotein from blood \& urine on at least 2 determinations for at least 6 weeks (WKs) by immunofixation studies, \<5% plasma cells in bone marrow on at least 1 determination, no increase in size/number of lytic bone lesions (LBLs) \& disappearance of soft tissue plasmacytomas (STP) for at least 6 WKs on skeletal survey (SS) if available) or partial response (PR: ≥50% reduction in serum M protein for at least 2 determinations 6 WKs apart, if present, reduction in 24-hour urinary light chain excretion by ≥90% or ≤200 mg for at least 2 determinations 6 WKs apart, ≥50% reduction in STP size for at least 6 WKs, \& no increase in size/number of LBLs on SS if available) as assessed by Independent Adjudication Committee (IAC) per European Blood \& Marrow Transplant (EBMT) criteria. To report RR \& 95% confidence intervals (CIs), exact test of binomial parameter was used.

  Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

Secondary Outcomes (7)

• Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 22 months

• Number of Participants Who Discontinued Study Treatment Due to an AE

  Up to approximately 18 months

• Time To Disease Progression (TTP) as Determined by IAC Per EBMT Criteria

  Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

• TTP as Assessed by Investigator Per EBMT Criteria

  Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

• Progression-Free Survival (PFS) as Determined by IAC Per EBMT Criteria

  Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

Study Arms (1)

Vorinostat + Bortezomib

EXPERIMENTAL

Participants receive vorinostat 400 mg, orally, once daily (QD) on Days 1-14 of each 21-day treatment cycle and bortezomib 1.3mg/m\^2 intravenous (IV) injection QD on Days 1, 4, 8 and 11 of each 21-day treatment cycle for up to 26 cycles. Participants with progressive disease (PD) after 2 cycles of treatment or no change (NC) after 4 cycles of treatment receive additional treatment of Dexamethasone, 20 mg of total daily dose, orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day treatment cycle for up to 26 cycles. Eligible participants could receive additional treatment on an extension.

Drug: Vorinostat; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Vorinostat DRUG

Four 100 mg vorinostat capsules orally, once daily (QD) by mouth on Days 1-14 of each 21-day treatment cycle.

Also known as: MK-0683, Suberoylanilide hydroxamic acid, Zolinza

Vorinostat + Bortezomib

Bortezomib DRUG

Bortezomib 1.3 mg/m\^2, IV injection QD on Days 1, 4, 8, and 11 of each 21-day treatment cycle.

Also known as: Velcade

Vorinostat + Bortezomib

Dexamethasone DRUG

Five 4 mg Dexamethasone tablets orally, QD on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day treatment cycle if PD is observed after 2 treatment cycles or if NC to disease is observed after 4 treatment cycles.

Also known as: Decadron

Vorinostat + Bortezomib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 27025160 RESULT

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Vorinostat; Bortezomib; Dexamethasone; Calcium Dobesilate

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)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: October 14, 2008
• First Posted: October 16, 2008
• Study Start: December 1, 2008
• Primary Completion: May 16, 2011
• Study Completion: April 9, 2012
• Last Updated: April 1, 2021
• Results First Posted: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share