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| ID | Type | Description | Link |
|---|---|---|---|
| MK-0683-098 | Other Identifier | Merck |
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The primary purpose of this clinical study is to determine the recommended clinical doses of vorinostat (MK-0683) and bortezomib administered in combination to participants with relapsed and/or refractory multiple myeloma (MM). It was hypothesized that administration of vorinostat in combination with bortezomib is sufficiently safe and tolerated well enough to permit further study in participants with relapsed and/or refractory MM. Study results are based on data collected up to the data cut-off date of 20-March-2011.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vorinostat + Bortezomib | Experimental | Participants undergo up to 3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg once daily [QD] on Days 1 through 14) + bortezomib (1.3 mg/m^2 intravenous [IV] on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vorinostat | Drug | Vorinostat (MK-0683) three or four 100 mg capsules taken by mouth with food. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1 | The number of participants with ≥1 DLT during Cycle 1 is reported. A DLT is defined as an event considered by the investigator to be related to study treatment, and either: 1) a Grade 3 or 4 non-hematologic event (except for manageable toxicity by supportive care or non-prohibited therapies, or a transient increase in alanine aminotransferase [ALT]/aspartate aminotransferase [AST]); or 2) a Grade 4 hematologic toxicity except neutropenia or hemoglobin decreased (neutropenia was a DLT if it was Grade 3-4 with fever ≥38.5°C; Grade 3-4 with an infection requiring antibiotic/antifungal therapy; or Grade 4 and lasting ≥5 days). | Up to 21 days |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With an Adverse Event (AE) | The number of participants with ≥1 AE is reported. An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product(s), whether or not considered related to the use of the product(s). | Up to 346 days (up to 30 days after the final dose of study treatment) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26619834 | Result | Ogawa Y, Ogura M, Tobinai K, Ando K, Suzuki T, Watanabe T, Ohmachi K, Uchida T, Hanson ME, Tanaka Y, Koh Y, Shimamoto T, Hotta T. A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma. Int J Hematol. 2016 Jan;103(1):25-33. doi: 10.1007/s12185-015-1897-7. Epub 2015 Nov 30. |
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Adult male and female participants with relapsed and/or refractory multiple myeloma (MM) were enrolled at study sites in Japan.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vorinostat + Bortezomib | Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Vorinostat + Bortezomib | Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1 | The number of participants with ≥1 DLT during Cycle 1 is reported. A DLT is defined as an event considered by the investigator to be related to study treatment, and either: 1) a Grade 3 or 4 non-hematologic event (except for manageable toxicity by supportive care or non-prohibited therapies, or a transient increase in alanine aminotransferase [ALT]/aspartate aminotransferase [AST]); or 2) a Grade 4 hematologic toxicity except neutropenia or hemoglobin decreased (neutropenia was a DLT if it was Grade 3-4 with fever ≥38.5°C; Grade 3-4 with an infection requiring antibiotic/antifungal therapy; or Grade 4 and lasting ≥5 days). | All treated participants who were not refractory to bortezomib and met all inclusion criteria are included. | Posted | Count of Participants | Participants | Up to 21 days |
|
Up to 346 days (up to 30 days after the final dose of study treatment)
All treated participants are included.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vorinostat + Bortezomib | Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
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| ID | Term |
|---|---|
| D000077337 | Vorinostat |
| D000069286 | Bortezomib |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
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| Bortezomib | Drug | Bortezomib (1.0 or 1.3 mg/m^2) intravenous infusion. |
|
|
| Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Vorinostat Administered With Bortezomib on Days 1 and 11 | The AUC0-24hr of vorinostat in plasma on Days 1 and 11 is reported in participants who also received bortezomib. | Predose and 0.8, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 1 and 11 |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Participants undergo ≤3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.3 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11).
|
|
| Other Pre-specified | Number of Participants With an Adverse Event (AE) | The number of participants with ≥1 AE is reported. An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product(s), whether or not considered related to the use of the product(s). | All treated participants are included. | Posted | Count of Participants | Participants | Up to 346 days (up to 30 days after the final dose of study treatment) |
|
|
|
| Other Pre-specified | Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Vorinostat Administered With Bortezomib on Days 1 and 11 | The AUC0-24hr of vorinostat in plasma on Days 1 and 11 is reported in participants who also received bortezomib. | Participants with data available are included. | Posted | Least Squares Mean | 95% Confidence Interval | µM*hr | Predose and 0.8, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 1 and 11 |
|
|
|
|
| 0 |
| 9 |
| 3 |
| 9 |
| 9 |
| 9 |
| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 13.1 | Systematic Assessment |
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| Conjunctivitis | Eye disorders | MedDRA 13.1 | Systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Gingival bleeding | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Gingivitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Malaise | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 13.1 | Systematic Assessment |
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| Drug-induced liver injury | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 13.1 | Systematic Assessment |
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| Enteritis infectious | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Hordeolum | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 13.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Blood albumin decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Blood glucose increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Blood phosphorus decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Blood potassium increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Electrocardiogram ST-T segment depression | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA 13.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hypercreatininaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 13.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 13.1 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 13.1 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 13.1 | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
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| Haemorrhage subcutaneous | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 13.1 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation.
| D014652 |
| Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D000588 |
| Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D001897 | Boronic Acids |
| D000148 | Acids, Noncarboxylic |
| D000143 | Acids |
| D007287 | Inorganic Chemicals |
| D001896 | Boron Compounds |
| D011719 | Pyrazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
|