Multiple Myeloma
Conditions
Brief summary
The purposes of this study are: * To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma * To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this combination, as determined per standard of care.
Interventions
DRUGvorinostat
Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).
DRUGbortezomib
Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults with refractory or relapsed multiple myeloma * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities) * Adequate bone marrow reserve * Adequate hepatic and renal function * Ability to swallow capsules * 3 weeks or more since prior chemotherapy and have recovered from prior toxicities
Exclusion criteria
* Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment * Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism * Participants with other active/uncontrolled clinically significant illness * Pregnant or nursing female participants * Participants who received bortezomib within 3 months of start of this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Duration of Treatment With Vorinostat | Day 1 to an event causing discontinuation from the study, assessed up to 29 months | Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity. Progressive disease was defined as: * \>25% increase in the level of serum monoclonal paraprotein. * 25% increase in 24-hour urinary light chain excretion. * \>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy. * Development of new bone lesions or soft tissue plasmacytomas. * Development of hypercalcemia. Intolerable toxicity was based on the clinical judgment of the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | Day 1 to disease progression, toxicity, or death, assessed up to 29 months | An adverse experience (AE) was 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 was temporally associated with the use of the sponsor's product, was also an adverse experience. |
| Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib | Day 1 to disease progression, toxicity, or death, assessed up to 29 months | An AE was 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 was temporally associated with the use of the sponsor's product, was also an adverse experience. |
| Clinical AE Summary | Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months) | An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose. |
| Laboratory AE Summary | Day 1 up to disease progression, toxicity, or death, assessed up to 29 months | An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose. A lab (S)AE was any lab value considered clinically significant in the investigator's judgment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Vorinostat capsules given 200 mg b.i.d., 300 mg q.d., or 400 mg q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break).
Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib 0.7 mg/m\^2, 0.9 mg/m\^2, 1.1 mg/m\^2, or 1.3 mg/m\^2 twice weekly on Days 1, 4, 8, and 11 or on Days 4, 8, 11, and 15 of each cycle, depending on dose level. | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 4 | 2 | 2 | 2 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Other | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Progressive disease | 2 | 1 | 5 | 3 | 4 | 3 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 60.6 years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 10 / 10 | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 1 / 3 | 2 / 10 | 4 / 6 | 4 / 6 | 2 / 6 |
Outcome results
Primary
Mean Duration of Treatment With Vorinostat
Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity. Progressive disease was defined as: * \>25% increase in the level of serum monoclonal paraprotein. * 25% increase in 24-hour urinary light chain excretion. * \>25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy. * Development of new bone lesions or soft tissue plasmacytomas. * Development of hypercalcemia. Intolerable toxicity was based on the clinical judgment of the investigator.
Time frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| All Participants | Mean Duration of Treatment With Vorinostat | 200 mg | 4.6 Days |
| All Participants | Mean Duration of Treatment With Vorinostat | 300 mg | 72.6 Days |
| All Participants | Mean Duration of Treatment With Vorinostat | 400 mg | 107.1 Days |
Secondary
Clinical AE Summary
An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.
Time frame: Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Clinical AE Summary | Who discontinued due to SAEs | 0 Participants |
| All Participants | Clinical AE Summary | With one or more AEs | 3 Participants |
| All Participants | Clinical AE Summary | With Serious AEs (SAEs) | 0 Participants |
| All Participants | Clinical AE Summary | Who discontinued due to drug-related SAEs | 0 Participants |
| All Participants | Clinical AE Summary | Who discontinued due to drug-related AEs | 0 Participants |
| All Participants | Clinical AE Summary | Who discontinued due to AEs | 1 Participants |
| All Participants | Clinical AE Summary | Who died | 0 Participants |
| All Participants | Clinical AE Summary | With no AEs | 0 Participants |
| All Participants | Clinical AE Summary | With drug-related SAEs | 0 Participants |
| All Participants | Clinical AE Summary | With drug-related AEs | 2 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to SAEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With drug-related AEs | 3 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related AEs | 2 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With drug-related SAEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related SAEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With one or more AEs | 3 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to AEs | 2 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who died | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With no AEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With Serious AEs (SAEs) | 1 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who died | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With drug-related SAEs | 1 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With one or more AEs | 10 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With no AEs | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With drug-related AEs | 10 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With Serious AEs (SAEs) | 2 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to AEs | 4 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related AEs | 3 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to SAEs | 1 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related SAEs | 1 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With no AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who died | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With Serious AEs (SAEs) | 4 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With one or more AEs | 6 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to AEs | 2 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related SAEs | 2 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related AEs | 2 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With drug-related SAEs | 4 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | Who discontinued due to SAEs | 2 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Clinical AE Summary | With drug-related AEs | 6 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | Who discontinued due to AEs | 1 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | With drug-related SAEs | 2 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | Who died | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | With no AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related AEs | 1 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | With drug-related AEs | 6 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | Who discontinued due to SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | With Serious AEs (SAEs) | 4 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Clinical AE Summary | With one or more AEs | 6 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With no AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to AEs | 2 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With drug-related SAEs | 1 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With drug-related AEs | 6 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to SAEs | 1 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With Serious AEs (SAEs) | 2 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who discontinued due to drug-related AEs | 1 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | With one or more AEs | 6 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Clinical AE Summary | Who died | 0 Participants |
Secondary
Laboratory AE Summary
An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition. A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose. A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.
Time frame: Day 1 up to disease progression, toxicity, or death, assessed up to 29 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Laboratory AE Summary | With laboratory Serious AEs (SAEs) | 0 Participants |
| All Participants | Laboratory AE Summary | With drug-related laboratory AEs | 1 Participants |
| All Participants | Laboratory AE Summary | Who discontinued due to drug-related lab SAEs | 0 Participants |
| All Participants | Laboratory AE Summary | Who discontinued due to laboratory SAEs | 0 Participants |
| All Participants | Laboratory AE Summary | Who discontinued due to drug-related lab AEs | 0 Participants |
| All Participants | Laboratory AE Summary | Who discontinued due to laboratory AEs | 0 Participants |
| All Participants | Laboratory AE Summary | With no laboratory AEs | 2 Participants |
| All Participants | Laboratory AE Summary | With one or more laboratory AEs | 1 Participants |
| All Participants | Laboratory AE Summary | Who died | 0 Participants |
| All Participants | Laboratory AE Summary | With drug-related laboratory SAEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With no laboratory AEs | 2 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With one or more laboratory AEs | 1 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With drug-related laboratory AEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With laboratory Serious AEs (SAEs) | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With drug-related laboratory SAEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who died | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory AEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab AEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory SAEs | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab SAEs | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With laboratory Serious AEs (SAEs) | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab AEs | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With one or more laboratory AEs | 3 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With drug-related laboratory SAEs | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With drug-related laboratory AEs | 2 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With no laboratory AEs | 7 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who died | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory SAEs | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab SAEs | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With no laboratory AEs | 6 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With one or more laboratory AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | Who died | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With drug-related laboratory SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With laboratory Serious AEs (SAEs) | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Laboratory AE Summary | With drug-related laboratory AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | With laboratory Serious AEs (SAEs) | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | With drug-related laboratory SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | Who died | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | With one or more laboratory AEs | 2 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | With drug-related laboratory AEs | 1 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Laboratory AE Summary | With no laboratory AEs | 4 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who died | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With no laboratory AEs | 3 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With drug-related laboratory AEs | 3 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With drug-related laboratory SAEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With laboratory Serious AEs (SAEs) | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to drug-related lab AEs | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | With one or more laboratory AEs | 3 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Laboratory AE Summary | Who discontinued due to laboratory SAEs | 0 Participants |
Secondary
Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib
An AE was 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 was temporally associated with the use of the sponsor's product, was also an adverse experience.
Time frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib | NA Days | — |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib | NA Days | — |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib | 58 Days | Standard Deviation 39 |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib | 58 Days | Standard Deviation 11 |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib | 128 Days | Standard Deviation 148 |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib | 32 Days | Standard Deviation 5 |
Secondary
Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug
An adverse experience (AE) was 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 was temporally associated with the use of the sponsor's product, was also an adverse experience.
Time frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Participants | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | One dose modification | 0 Participants |
| All Participants | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | No dose modification | 3 Participants |
| All Participants | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | Two or more dose modifications | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | One dose modification | 0 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | No dose modification | 3 Participants |
| Vorinostat 200 mg + Bortezomib 0.9 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | Two or more dose modifications | 0 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | One dose modification | 2 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | No dose modification | 8 Participants |
| Vorinostat 300 mg + Bortezomib 1.3 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | Two or more dose modifications | 0 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | One dose modification | 2 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | No dose modification | 4 Participants |
| Vorinostat 400 mg + Bortezomib 0.9 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | Two or more dose modifications | 0 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | One dose modification | 1 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | No dose modification | 3 Participants |
| Vorinostat 400 mg + Bortezomib 1.1 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | Two or more dose modifications | 2 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | No dose modification | 3 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | Two or more dose modifications | 3 Participants |
| Vorinostat 400 mg + Bortezomib 1.3 mg/m^2 | Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug | One dose modification | 0 Participants |