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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)

Completed Phase 2 Results posted Last updated 1 April 2021
What this trial tests

Phase 2 trial testing Vorinostat in Relapsed or Refractory Multiple Myeloma in 143 participants. Completed in 9 April 2012.

Timeline
1 December 2008
Primary endpoint
16 May 2011
9 April 2012

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment143
Start date1 December 2008
Primary completion16 May 2011
Estimated completion9 April 2012

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Relapsed or Refractory Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (RR) Primary · Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

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-

GroupValue95% CI
Vorinostat + Bortezomib11.36.6 – 17.7
Number of Participants Who Experienced an Adverse Event (AE) Secondary · Up to approximately 22 months

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experienced an AE were reported.

GroupValue95% CI
Vorinostat + Bortezomib142
Number of Participants Who Discontinued Study Treatment Due to an AE Secondary · Up to approximately 18 months

An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinued study treatment due to an AE were reported.

GroupValue95% CI
Vorinostat + Bortezomib28
Time To Disease Progression (TTP) as Determined by IAC Per EBMT Criteria Secondary · Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

TTP was defined as the time from allocation to the first documented disease progression (PD) as determined by IAC per EBMT criteria or death due to myeloma, whichever occurred first. PD: \>25% increase in level of serum Mparaprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or \>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must

GroupValue95% CI
Vorinostat + Bortezomib3.472.53 – 4.57
TTP as Assessed by Investigator Per EBMT Criteria Secondary · Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

TTP was defined as the time from allocation to the first documented PD as assessed by investigator per EBMT criteria or death due to myeloma, whichever occurred first. PD: \>25% increase in level of serum Mparaprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or \>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an abso

GroupValue95% CI
Vorinostat + Bortezomib3.072.37 – 4.33
Progression-Free Survival (PFS) as Determined by IAC Per EBMT Criteria Secondary · Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

PFS was defined as the time from allocation to the first documents PD as determined by IAC per EBMT criteria or death due to any cause, whichever occurs first. PD: \>25% increase in level of serum M-paraprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or \>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute in

GroupValue95% CI
Vorinostat + Bortezomib3.132.40 – 4.33
PFS as Assessed by Investigator Per EBMT Criteria Secondary · Up to approximately 30 months (through Final Analysis data cut-off of 16-May-2011)

PFS was defined as the time from allocation to the first documents PD as assessed by investigator per EBMT criteria or death due to any cause, whichever occurs first. PD: \>25% increase in level of serum M-paraprotein, which must also be an absolute increase of at least 5g/L (500 mg/dL) and confirmed on a repeat investigation or 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg/24hour and confirmed on a repeat investigation or \>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an abso

GroupValue95% CI
Vorinostat + Bortezomib2.832.17 – 3.77
Overall Survival (OS) Secondary · Up to approximately 40 months (through End of Trial data cut-off of 09-Apr-2012)

OS was defined as the time from allocation to death due to any cause. To report the median survival (in months) and the associated 95%CIs were reported using Kaplan-Meier method was used. Participants without documented death at the time of final analysis were censored at the date of the last follow up.

GroupValue95% CI
Vorinostat + Bortezomib11.238.47 – 14.43

Adverse events — posted to ClinicalTrials.gov

Time frame: Up tp approximately 22 months for non-serious adverse events (AEs). Up to approximately 40 months for serious AEs and all-cause mortality.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vorinostat + Bortezomib
Serious: 92/142 (65%)
Deaths: 85/143

Serious adverse events (103 terms)

ReactionSystemVorinostat + Bortezomib
Neoplasm malignantNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumoniaInfections and infestations
Accidental overdoseInjury, poisoning and procedural complications
Renal failure acuteRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
SepsisInfections and infestations
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Lower respiratory tract infectionInfections and infestations
NauseaGastrointestinal disorders
GastroenteritisInfections and infestations
Lung infectionInfections and infestations
Pneumocystis jiroveci pneumoniaInfections and infestations
Septic shockInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
HypercalcaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Renal failureRenal and urinary disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Pulmonary oedemaRespiratory, thoracic and mediastinal disorders
Hyperviscosity syndromeBlood and lymphatic system disorders
Other adverse events (53 terms — click to expand)

ReactionSystemVorinostat + Bortezomib
ThrombocytopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
HeadacheNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
Back painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Blood creatinine increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
Upper respiratory tract infectionInfections and infestations
Neuropathy peripheralNervous system disorders
Platelet count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
NasopharyngitisInfections and infestations
NeuralgiaNervous system disorders
HypotensionVascular disorders
Chest painGeneral disorders
Weight decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
HypertensionVascular disorders
Abdominal pain upperGastrointestinal disorders
ChillsGeneral disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Vision blurredEye disorders
DyspepsiaGastrointestinal disorders

Most-reported serious reactions: Neoplasm malignant, Pneumonia, Accidental overdose, Renal failure acute, Diarrhoea, Pyrexia, Thrombocytopenia, Asthenia.

Data from ClinicalTrials.gov NCT00773838 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
    Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
  2. Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma.
    Hideshima T, Richardson PG, Anderson KC. · · 2011 · cited 216× · PMID 22072815 · DOI 10.1158/1535-7163.mct-11-0433
  3. Trials with 'epigenetic' drugs: an update.
    Nebbioso A, Carafa V, Benedetti R, Altucci L. · · 2012 · cited 162× · PMID 23103179 · DOI 10.1016/j.molonc.2012.09.004
  4. Immunoepigenetics Combination Therapies: An Overview of the Role of HDACs in Cancer Immunotherapy.
    Banik D, Moufarrij S, Villagra A. · · 2019 · cited 96× · PMID 31067680 · DOI 10.3390/ijms20092241
  5. Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.
    Zhao A, Zhou H, Yang J, Li M, et al · · 2023 · cited 81× · PMID 36797244 · DOI 10.1038/s41392-023-01342-6
  6. Modulation of antigen-presenting cells by HDAC inhibitors: implications in autoimmunity and cancer.
    Woan KV, Sahakian E, Sotomayor EM, Seto E, et al · · 2012 · cited 54× · PMID 22105512 · DOI 10.1038/icb.2011.96
  7. Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives.
    Pu J, Liu T, Wang X, Sharma A, et al · · 2024 · cited 36× · PMID 38654286 · DOI 10.1186/s40164-024-00507-5
  8. VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Relapsed and Refractory Multiple Myeloma.
    Siegel DS, Dimopoulos M, Jagannath S, Goldschmidt H, et al · · 2016 · cited 20× · PMID 27025160 · DOI 10.1016/j.clml.2016.02.042

Verify or expand the search:

Other trials of Vorinostat

Trials testing the same drug.

Other recruiting trials for Relapsed or Refractory Multiple Myeloma

Currently open trials in the same condition.

Other Merck Sharp & Dohme LLC trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing