Multiple Myeloma
Conditions
Brief summary
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.
Interventions
DRUGVorinostat
Vorinostat (MK-0683) three or four 100 mg capsules taken by mouth with food.
DRUGBortezomib
Bortezomib (1.0 or 1.3 mg/m\^2) intravenous infusion.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* is ≥20 years of age. * has an established diagnosis of MM based on the myeloma diagnostic criteria * has received at least 1 but not more than 3 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen * has adequate organ function
Exclusion criteria
* has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone marrow transplantation during the study * has known hypersensitivity to any components of vorinostat or bortezomib * has active hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus (HIV) positive * has had prior treatment with vorinostat or histone deacetylase (HDAC) inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1 | Up to 21 days | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Adverse Event (AE) | Up to 346 days (up to 30 days after the final dose of study treatment) | 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). |
| 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 | 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 | The AUC0-24hr of vorinostat in plasma on Days 1 and 11 is reported in participants who also received bortezomib. |
Participant flow
Recruitment details
Adult male and female participants with relapsed and/or refractory multiple myeloma (MM) were enrolled at study sites in Japan.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Progressive disease | 2 |
| Overall Study | Status unknown | 1 |
Baseline characteristics
| Characteristic | Vorinostat + Bortezomib |
|---|---|
| Age, Continuous | 63.3 Years STANDARD_DEVIATION 11.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 3 / 9 |
Outcome results
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).
Time frame: Up to 21 days
Population: All treated participants who were not refractory to bortezomib and met all inclusion criteria are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorinostat + Bortezomib | Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1 | 1 Participants |
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.
Time frame: 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
Population: Participants with data available are included.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Vorinostat + Bortezomib | 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 | Day 1 | 5.41 µM*hr |
| Vorinostat + Bortezomib | 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 | Day 11 | 5.84 µM*hr |
90% CI: [0.8, 1.45]
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).
Time frame: Up to 346 days (up to 30 days after the final dose of study treatment)
Population: All treated participants are included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vorinostat + Bortezomib | Number of Participants With an Adverse Event (AE) | 9 Participants |