Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
Relapsed/refractory multiple myeloma, Relapsed multiple myeloma, Refractory multiple myeloma, Multiple myeloma
Brief summary
This was a Phase 3, multicenter, randomized, double blind, placebo-controlled study evaluating the efficacy and safety of venetoclax plus bortezomib and dexamethasone in participants with relapsed or refractory multiple myeloma who are considered sensitive or naïve to proteasome inhibitors and received 1 to 3 prior lines of therapy for multiple myeloma.
Interventions
DRUGVenetoclax
Participants self-administered venetoclax tablets by mouth QD in combination with bortezomib. Venetoclax was to be given before other agents administered on the same day, if applicable. Each venetoclax dose was to be taken all at one time with approximately 240 mL of water within 30 minutes after completion of breakfast or the subject's first meal of the day. Tablets were to be swallowed whole and must not have been broken, chewed, or crushed. On days that pre-dose PK sampling was required, dosing occurred at the clinic to facilitate PK sampling.
DRUGBortezomib
Bortezomib (subcutaneous injection \[preferred\] or IV) was given following administration of venetoclax or placebo in Cycles 1 -8 on Days 1, 4, 8 and 11, and for Cycles 9 and beyond, on Days 1, 8, 15 and 22 and was to be administered per the prescribing information. The route of administration was to stay the same during the study.
DRUGDexamethasone
Dexamethasone was to be given orally, administered per the prescribing information, the day of bortezomib dosing and the following day, given the protocol-defined dosing window (bortezomib dosing window is ± 1 day) is maintained. If bortezomib was interrupted or a dose is skipped, dexamethasone was to be administered as scheduled per protocol (unless dexamethasone was interrupted due to toxicity).
DRUGPlacebo for venetoclax
Participants self-administered placebo tablets by mouth QD in combination with bortezomib. Placebo was to be given before other agents administered on the same day, if applicable. Each placebo dose was to be taken all at one time with approximately 240 mL of water within 30 minutes after completion of breakfast or the subject's first meal of the day. Tablets were to be swallowed whole and must not have been broken, chewed, or crushed. On days that pre-dose PK sampling was required, dosing occurred at the clinic to facilitate PK sampling.
Sponsors
Genentech, Inc.
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 * Participant has documented relapsed or progressive multiple myeloma on or after any regimen or who are refractory to the most recent line of therapy. Relapsed myeloma is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, but does not meet the criteria for refractory myeloma. Refractory myeloma is defined as disease that is nonresponsive (failure to achieve minimal response or development of progressive disease \[PD\]) while on primary or salvage therapy, or progresses within 60 days of last therapy. * Participant must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma. A line of therapy consists of ≥ 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens. * Prior treatment with bortezomib or other proteasome inhibitor is allowed, provided ALL of the following criteria are met: Disease is NOT refractory to any proteasome inhibitor, defined as no disease progression (i.e., PD, per International Myeloma Working Group \[IMWG\] or European Society for Blood and Marrow Transplantation \[EBMT\] criteria) while receiving proteasome inhibitor therapy or within 60 days after the last dose, AND best response achieved with any proteasome inhibitor therapy (alone or in combination) was at least a Partial Response (PR), AND participant did not discontinue any proteasome inhibitor due to intolerance or ≥ Grade 3 related toxicity. * Participant has measurable disease at Screening, defined as at least one of the following: Serum M-protein ≥ 0.5 g/dL, OR Urine M-protein ≥ 200 mg in 24-hours, OR serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.
Exclusion criteria
* Participant is refractory to any proteasome inhibitor, defined as progression on or within 60 days of the last dose of a proteasome inhibitor-containing regimen. * Participant has had prior treatment with proteasome inhibitor within 60 days prior to first dose of study drug. * Participant has any of the following conditions: Non-secretory multiple myeloma, active plasma cell leukemia i.e., either 20% of peripheral white blood cells or greater than 2.0 X 10\^9/liter (L) circulating plasma cells by standard differential, Waldenstrom's macroglobulinemia, amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), known Human Immunodeficiency Viral (HIV) infection, active hepatitis B or C infection based on blood screen tests, significant cardiovascular disease, including uncontrolled angina, severe or uncontrolled arrhythmia, recent myocardial infarction within 6 months of randomization, or congestive heart failure New York Heart Association (NYHA) Class ≥ 3, major surgery within 4 weeks prior to randomization, acute infections requiring parenteral therapy (antibiotic, antifungal, or antiviral) within 14 days prior to randomization, peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to randomization, uncontrolled diabetes or uncontrolled hypertension within 14 days prior to randomization, any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study * Participant has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions: Adequately treated in situ carcinoma of the cervix uteri or the breast, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment, previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study * If participant had prior allogeneic stem cell transplant (SCT), participant has evidence of ongoing graft-versus-host disease (GvHD)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group | PFS is defined as the number of days from the date the participant was randomized to the date of the first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to any cause, whichever occurs first. PFS was analyzed by Kaplan-Meier methodology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) in Participants With High B-cell Lymphoma 2 (BCL-2) Expression | Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group | PFS is defined as the number of days from the date the participant was randomized to the date of the first documented progressive disease (PD) per investigator assessment or death due to any cause, whichever occurs first. PFS was analyzed by Kaplan-Meier methodology. BCL-2 expression was determined through central laboratory testing by immunohistochemistry (IHC) and based on a pre-specified scoring algorithm. High clinical score of 2+: ≥50% of tumor cells with moderate or higher cytoplasmic staining but \< 50% of tumor cells with strong staining intensity; high clinical score of 3+: ≥50% of tumor cells with strong cytoplasmic staining. |
| Duration of Response (DOR) | Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group | DOR is defined as the number of days from the participant's date of first documented response (partial response \[PR\] or better) to the date of first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to multiple myeloma, whichever occurs first. DOR was analyzed by Kaplan-Meier methodology. |
| Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment | The BPI-SF is a pain-specific measure developed to assess patient-reported severity (or intensity) of pain (4 items) and the impact of pain on daily functioning (7 items) in patients with cancer pain. The four pain severity items assess pain at its worst in last 24 hours, least in last 24 hours, average, and now (current pain). For these items, participants are asked to rate their pain on an 11-point numeric rating scale with anchors of 0 (no pain) and 10 (pain as bad as you can imagine). The Worst Pain scores range from 0 to 10, with higher scores indicating severe pain. Negative changes from baseline indicate improvement. |
| Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment | The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For the Physical Functioning scale, participants rate five items on a four-point scale, with 1 as not at all and 4 as very much. The Physical Functioning Scale scores range from 0 to 100 and were calculated per the EORTC QLQ-C30 Scoring Manual (3rd edition), version 3.0. A high scale score represents high/healthy level of functioning. Positive changes from baseline indicate improvement. |
| Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment | The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For the Global Health Status/Quality of Life scale, participants rate two items on a seven point scale, with 1 as very poor and 7 as excellent. The Global Health Status/Quality of Life scale ranges from 0 to 100 and was calculated per the EORTC QLQ-C30 Scoring Manual (3rd edition), version 3.0. A high score for the global health status/QoL represents a high QoL. Positive changes from baseline indicate improvement. |
| Very Good Partial Response (VGPR) or Better Response Rate | Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group | The percentage of participants with documented best overall response of Very Good Partial Response (VGPR) or better (VGPR, Complete response \[CR\], or Stringent complete response \[sCR\]) per 2016 standard International Myeloma Working Group (IMWG) criteria as determined by an Independent Review Committee (IRC) was computed. |
| Overall Survival (OS). | Median duration of follow-up was 45.6 months for the venetoclax group and 45.6 months for the placebo group | OS is defined as the number of days from the date of randomization to the date of death due to any cause. All events of death were to be included, regardless of whether the event occurred while the participant was still taking study drug or after the participant discontinued study drug. If a participant is not known to have died, OS was censored at the date of last contact. The distribution of OS was estimated using Kaplan-Meier methodology. |
| Time to Progression (TTP) | Median time on follow-up up was 28.6 months for the venetoclax group and 28.6 months for the placebo group | TTP is defined as the number of days from the date of randomization to the date of first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to multiple myeloma, whichever occurs first. TTP was analyzed by Kaplan-Meier methodology. |
| Overall Response Rate (ORR) | Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group | Overall response rate is defined as the percentage of participants with documented best overall response of Partial Response (PR) or better (PR, Very good partial response \[VGPR\], Complete response \[CR\], or Stringent complete response \[sCR\]) per International Myeloma Working Group (IMWG) criteria as determined by an Independent Review Committee (IRC). |
| Minimal Residual Disease (MRD) Negativity Rate | Assessed at Screening; to confirm a stringent Complete Response (sCR) or Complete Response (CR); at 6 months and 12 months post-confirmed CR/sCR | MRD negativity rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any time point after randomization and before progression or starting subsequent therapy. MRD negativity was defined at 10\^-5 threshold (less than one residual myeloma cell per 10\^5 total nucleated cells) as measured by centralized testing of bone marrow aspirate by Next Generation Sequencing (NGS). MRD positive participants include those of which all tested samples were found to be MRD positive or indeterminate. Participants with missing or unevaluable MRD status were considered as MRD positive. |
| Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment | PROMIS Cancer Fatigue SF is a seven item questionnaire that assesses the impact and experience of fatigue over the past 7 days. All questions employ the following five response options: 1 = Not at all, 2 = A little bit, 3 = Somewhat, 4 = Quite a bit, and 5 = Very much. The total raw score is the sum of the responses to each question and is converted to a T-score. The T-score re-scales the total raw score to a standardized score with a mean of 50 and a standard deviation of 10. The \[PROMIS\] Cancer Fatigue Short Form \[SF\] 7a T-Scores range from 29.4 to 83.2, with higher scores indicating more fatigue. Negative changes from baseline indicate improvement. |
Countries
Australia, Brazil, Canada, France, Germany, Hungary, Ireland, Italy, Japan, Russia, South Korea, Spain, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
Participants by arm
| Arm | Count |
|---|---|
| Venetoclax + Bortezomib and Dexamethasone Cycles 1-8: Venetoclax 800 mg orally every day (QD) on Days 1 - 21 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 4, 8 & 11 and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 & 12; Cycles 9 and beyond: Venetoclax 800 mg orally every day (QD) on Days 1 - 35 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 8, 15 and 22 and dexamethasone 20 mg orally on Days 1, 2, 8, 9, 15, 16, 22 and 23 | 194 |
| Placebo + Bortezomib and Dexamethasone Cycles 1-8: Placebo (to match venetoclax 100 mg tablet) 800 mg orally every day (QD) on Days 1 - 21 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 4, 8 & 11 and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11 & 12; Cycles 9 and beyond: Placebo (to match venetoclax 100 mg tablet) 800 mg orally every day (QD) on Days 1 - 35 plus bortezomib 1.3 mg/m\^2 subcutaneously or IV on Days 1, 8, 15 and 22 and dexamethasone 20 mg orally on Days 1, 2, 8, 9, 15, 16, 22 & 23 | 97 |
| Total | 291 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 78 | 36 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other, not specified | 20 | 3 |
| Overall Study | Participant missing reason for study discontinuation | 1 | 0 |
| Overall Study | Study terminated by Sponsor | 67 | 47 |
| Overall Study | Withdrew consent | 27 | 11 |
Baseline characteristics
| Characteristic | Venetoclax + Bortezomib and Dexamethasone | Total | Placebo + Bortezomib and Dexamethasone |
|---|---|---|---|
| Age, Continuous | 65.9 years STANDARD_DEVIATION 9.41 | 65.9 years STANDARD_DEVIATION 8.9 | 65.9 years STANDARD_DEVIATION 7.81 |
| Chromosomal abnormality (CA) risk by fluorescent in situ hybridization (FISH) High | 31 Participants | 49 Participants | 18 Participants |
| Chromosomal abnormality (CA) risk by fluorescent in situ hybridization (FISH) MISSING | 13 Participants | 16 Participants | 3 Participants |
| Chromosomal abnormality (CA) risk by fluorescent in situ hybridization (FISH) Standard | 141 Participants | 213 Participants | 72 Participants |
| Chromosomal abnormality (CA) risk by fluorescent in situ hybridization (FISH) Unknown | 9 Participants | 13 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 32 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 169 Participants | 259 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Multiple myeloma International Staging System(ISS) stage MISSING | 0 Participants | 1 Participants | 1 Participants |
| Multiple myeloma International Staging System(ISS) stage Not evaluable | 5 Participants | 8 Participants | 3 Participants |
| Multiple myeloma International Staging System(ISS) stage Stage I | 81 Participants | 129 Participants | 48 Participants |
| Multiple myeloma International Staging System(ISS) stage Stage II | 69 Participants | 101 Participants | 32 Participants |
| Multiple myeloma International Staging System(ISS) stage Stage III | 39 Participants | 52 Participants | 13 Participants |
| Number of prior lines of multiple myeloma therapy 1 line | 91 Participants | 135 Participants | 44 Participants |
| Number of prior lines of multiple myeloma therapy 2-3 lines | 103 Participants | 156 Participants | 53 Participants |
| Number of prior lines of therapy | 1.0 number of prior lines of therapy | 1.0 number of prior lines of therapy | 2.0 number of prior lines of therapy |
| Prior exposure to an anti-CD38 monoclonal antibody MISSING | 4 Participants | 5 Participants | 1 Participants |
| Prior exposure to an anti-CD38 monoclonal antibody Naïve | 185 Participants | 280 Participants | 95 Participants |
| Prior exposure to an anti-CD38 monoclonal antibody Refractory | 5 Participants | 6 Participants | 1 Participants |
| Prior exposure to an anti-CD38 monoclonal antibody Sensitive | 0 Participants | 0 Participants | 0 Participants |
| Prior exposure to an anti-CD38 monoclonal antibody Unknown | 0 Participants | 0 Participants | 0 Participants |
| Prior exposure to an immunomodulatory drug (IMID) MISSING | 0 Participants | 1 Participants | 1 Participants |
| Prior exposure to an immunomodulatory drug (IMID) Naïve | 63 Participants | 93 Participants | 30 Participants |
| Prior exposure to an immunomodulatory drug (IMID) Refractory | 64 Participants | 100 Participants | 36 Participants |
| Prior exposure to an immunomodulatory drug (IMID) Sensitive | 67 Participants | 96 Participants | 29 Participants |
| Prior exposure to an immunomodulatory drug (IMID) Unknown | 0 Participants | 1 Participants | 1 Participants |
| Prior exposure to proteasome inhibitors (PI) MISSING | 0 Participants | 1 Participants | 1 Participants |
| Prior exposure to proteasome inhibitors (PI) Naïve | 61 Participants | 89 Participants | 28 Participants |
| Prior exposure to proteasome inhibitors (PI) Refractory | 0 Participants | 2 Participants | 2 Participants |
| Prior exposure to proteasome inhibitors (PI) Sensitive | 131 Participants | 197 Participants | 66 Participants |
| Prior exposure to proteasome inhibitors (PI) Unknown | 2 Participants | 2 Participants | 0 Participants |
| Prior stem cell transplant Allogeneic | 2 Participants | 2 Participants | 0 Participants |
| Prior stem cell transplant Autologous | 114 Participants | 171 Participants | 57 Participants |
| Prior stem cell transplant MISSING | 78 Participants | 118 Participants | 40 Participants |
| Prior stem cell transplant Syngeneic | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 59 Participants | 87 Participants | 28 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 12 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 124 Participants | 190 Participants | 66 Participants |
| Sex: Female, Male Female | 97 Participants | 139 Participants | 42 Participants |
| Sex: Female, Male Male | 97 Participants | 152 Participants | 55 Participants |
| Time since diagnosis | 1263.5 days | 1318.0 days | 1461.0 days |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 81 / 194 | 36 / 97 |
| other Total, other adverse events | 191 / 193 | 95 / 96 |
| serious Total, serious adverse events | 115 / 193 | 53 / 96 |
Outcome results
Primary
Progression-free Survival (PFS)
PFS is defined as the number of days from the date the participant was randomized to the date of the first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to any cause, whichever occurs first. PFS was analyzed by Kaplan-Meier methodology.
Time frame: Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Progression-free Survival (PFS) | 23.2 months |
| Placebo + Bortezomib and Dexamethasone | Progression-free Survival (PFS) | 11.5 months |
Comparison: Stratified Analysis; Stratification factors: Prior exposure to proteasome inhibitors (naïve versus sensitive), and number of prior lines of therapy (1 versus 2 or 3)p-value: =0.01295% CI: [0.471, 0.913]Log Rank
Secondary
Duration of Response (DOR)
DOR is defined as the number of days from the participant's date of first documented response (partial response \[PR\] or better) to the date of first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to multiple myeloma, whichever occurs first. DOR was analyzed by Kaplan-Meier methodology.
Time frame: Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Duration of Response (DOR) | NA months |
| Placebo + Bortezomib and Dexamethasone | Duration of Response (DOR) | 12.8 months |
Comparison: Stratified Analysis; Stratification factors: Prior exposure to proteasome inhibitors (naïve versus sensitive), and number of prior lines of therapy (1 versus 2 or 3)p-value: <0.00195% CI: [0.343, 0.753]Log Rank
Secondary
Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain
The BPI-SF is a pain-specific measure developed to assess patient-reported severity (or intensity) of pain (4 items) and the impact of pain on daily functioning (7 items) in patients with cancer pain. The four pain severity items assess pain at its worst in last 24 hours, least in last 24 hours, average, and now (current pain). For these items, participants are asked to rate their pain on an 11-point numeric rating scale with anchors of 0 (no pain) and 10 (pain as bad as you can imagine). The Worst Pain scores range from 0 to 10, with higher scores indicating severe pain. Negative changes from baseline indicate improvement.
Time frame: Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization; participants who have both baseline and post-baseline values are included in the analysis at each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 15, Day 1 | -0.2 units on a scale | Standard Deviation 2.92 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 5, Day 1 | 0.0 units on a scale | Standard Deviation 2.65 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 7, Day 1 | -0.1 units on a scale | Standard Deviation 2.56 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 9, Day 1 | -0.2 units on a scale | Standard Deviation 3.11 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 11, Day 1 | -0.4 units on a scale | Standard Deviation 2.57 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 13, Day 1 | -0.2 units on a scale | Standard Deviation 2.71 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 3, Day 1 | -0.6 units on a scale | Standard Deviation 2.59 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 17, Day 1 | -0.3 units on a scale | Standard Deviation 2.54 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 19, Day 1 | -0.1 units on a scale | Standard Deviation 2.59 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 21, Day 1 | -0.1 units on a scale | Standard Deviation 2.39 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 23, Day 1 | -0.0 units on a scale | Standard Deviation 3.2 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 25, Day 1 | 0.4 units on a scale | Standard Deviation 2.65 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 27, Day 1 | 0.2 units on a scale | Standard Deviation 2.53 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 29, Day 1 | -0.2 units on a scale | Standard Deviation 2.83 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 31, Day 1 | 0.0 units on a scale | Standard Deviation 3.11 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 33, Day 1 | -0.2 units on a scale | Standard Deviation 2.88 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 35, Day 1 | 0.1 units on a scale | Standard Deviation 2.77 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 37, Day 1 | 0.4 units on a scale | Standard Deviation 2.78 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 39, Day 1 | 0.1 units on a scale | Standard Deviation 2.7 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 41, Day 1 | 0.1 units on a scale | Standard Deviation 3 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 43, Day 1 | -0.1 units on a scale | Standard Deviation 3.07 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 45, Day 1 | -0.7 units on a scale | Standard Deviation 3.64 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 47, Day 1 | -2.8 units on a scale | Standard Deviation 3.77 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Final visit | 0.3 units on a scale | Standard Deviation 3.28 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 47, Day 1 | 1.0 units on a scale | — |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 3, Day 1 | -0.5 units on a scale | Standard Deviation 2.46 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 27, Day 1 | 0.1 units on a scale | Standard Deviation 1.92 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 5, Day 1 | -0.2 units on a scale | Standard Deviation 3.15 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 39, Day 1 | -0.3 units on a scale | Standard Deviation 1.15 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 7, Day 1 | 0.2 units on a scale | Standard Deviation 2.98 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 29, Day 1 | 0.3 units on a scale | Standard Deviation 2.15 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 9, Day 1 | 0.0 units on a scale | Standard Deviation 2.88 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 45, Day 1 | 1.0 units on a scale | Standard Deviation 0 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 11, Day 1 | 0.1 units on a scale | Standard Deviation 3.45 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 31, Day 1 | 0.6 units on a scale | Standard Deviation 1.33 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 13, Day 1 | -0.1 units on a scale | Standard Deviation 3.22 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 41, Day 1 | 0.3 units on a scale | Standard Deviation 1.15 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 15, Day 1 | -0.0 units on a scale | Standard Deviation 3.08 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 33, Day 1 | 0.4 units on a scale | Standard Deviation 1.4 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 17, Day 1 | -0.1 units on a scale | Standard Deviation 2.06 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Final visit | 0.4 units on a scale | Standard Deviation 3.55 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 19, Day 1 | -0.2 units on a scale | Standard Deviation 1.95 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 35, Day 1 | -0.2 units on a scale | Standard Deviation 1.33 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 21, Day 1 | -0.3 units on a scale | Standard Deviation 2.89 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 43, Day 1 | 0.5 units on a scale | Standard Deviation 0.71 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 23, Day 1 | -0.2 units on a scale | Standard Deviation 2.61 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 37, Day 1 | 1.5 units on a scale | Standard Deviation 2.65 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF) Worst Pain | Cycle 25, Day 1 | 0.2 units on a scale | Standard Deviation 3 |
Secondary
Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For the Global Health Status/Quality of Life scale, participants rate two items on a seven point scale, with 1 as very poor and 7 as excellent. The Global Health Status/Quality of Life scale ranges from 0 to 100 and was calculated per the EORTC QLQ-C30 Scoring Manual (3rd edition), version 3.0. A high score for the global health status/QoL represents a high QoL. Positive changes from baseline indicate improvement.
Time frame: Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization; participants who have both baseline and post-baseline values are included in the analysis at each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 15, Day 1 | -4.9 units on a scale | Standard Deviation 26.09 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 5, Day 1 | -5.1 units on a scale | Standard Deviation 26.74 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 7, Day 1 | -8.3 units on a scale | Standard Deviation 26.76 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 9, Day 1 | -6.9 units on a scale | Standard Deviation 26.33 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 11, Day 1 | -0.5 units on a scale | Standard Deviation 25.58 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 13, Day 1 | -1.0 units on a scale | Standard Deviation 25.05 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 3, Day 1 | -1.9 units on a scale | Standard Deviation 22.75 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 17, Day 1 | -5.1 units on a scale | Standard Deviation 24.91 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 19, Day 1 | -1.3 units on a scale | Standard Deviation 19.51 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 21, Day 1 | -6.6 units on a scale | Standard Deviation 26.16 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 23, Day 1 | -2.9 units on a scale | Standard Deviation 23.2 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 25, Day 1 | -4.7 units on a scale | Standard Deviation 26.29 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 27, Day 1 | -9.0 units on a scale | Standard Deviation 24.46 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 29, Day 1 | -6.9 units on a scale | Standard Deviation 24.67 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 31, Day 1 | -4.8 units on a scale | Standard Deviation 26.48 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 33, Day 1 | -7.7 units on a scale | Standard Deviation 27.22 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 35, Day 1 | -3.8 units on a scale | Standard Deviation 24.03 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 37, Day 1 | -13.7 units on a scale | Standard Deviation 29.86 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 39, Day 1 | -9.3 units on a scale | Standard Deviation 28.05 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 41, Day 1 | -11.0 units on a scale | Standard Deviation 30.47 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 43, Day 1 | 2.0 units on a scale | Standard Deviation 28.95 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 45, Day 1 | -1.7 units on a scale | Standard Deviation 33.75 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 47, Day 1 | 10.4 units on a scale | Standard Deviation 22.95 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Final visit | -8.1 units on a scale | Standard Deviation 26.4 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 47, Day 1 | -8.3 units on a scale | — |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 3, Day 1 | -2.2 units on a scale | Standard Deviation 22.63 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 27, Day 1 | 4.2 units on a scale | Standard Deviation 26.7 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 5, Day 1 | -2.5 units on a scale | Standard Deviation 23.54 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 39, Day 1 | 0.0 units on a scale | Standard Deviation 0 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 7, Day 1 | -6.7 units on a scale | Standard Deviation 24.56 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 29, Day 1 | -1.1 units on a scale | Standard Deviation 26.33 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 9, Day 1 | -6.7 units on a scale | Standard Deviation 24.22 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 45, Day 1 | 4.2 units on a scale | Standard Deviation 5.89 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 11, Day 1 | -5.2 units on a scale | Standard Deviation 25.38 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 31, Day 1 | 5.6 units on a scale | Standard Deviation 35.36 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 13, Day 1 | -1.7 units on a scale | Standard Deviation 22.24 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 41, Day 1 | 8.3 units on a scale | Standard Deviation 8.33 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 15, Day 1 | 0.5 units on a scale | Standard Deviation 23.56 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 33, Day 1 | -7.1 units on a scale | Standard Deviation 22.79 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 17, Day 1 | -7.7 units on a scale | Standard Deviation 21.55 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Final visit | -6.7 units on a scale | Standard Deviation 28.5 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 19, Day 1 | 0.8 units on a scale | Standard Deviation 26.09 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 35, Day 1 | 4.2 units on a scale | Standard Deviation 29.23 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 21, Day 1 | -5.6 units on a scale | Standard Deviation 20.01 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 43, Day 1 | -8.3 units on a scale | Standard Deviation 23.57 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 23, Day 1 | -1.0 units on a scale | Standard Deviation 22.99 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 37, Day 1 | 10.4 units on a scale | Standard Deviation 12.5 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Global Health Status/Quality of Life Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 25, Day 1 | -4.5 units on a scale | Standard Deviation 24.68 |
Secondary
Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score
PROMIS Cancer Fatigue SF is a seven item questionnaire that assesses the impact and experience of fatigue over the past 7 days. All questions employ the following five response options: 1 = Not at all, 2 = A little bit, 3 = Somewhat, 4 = Quite a bit, and 5 = Very much. The total raw score is the sum of the responses to each question and is converted to a T-score. The T-score re-scales the total raw score to a standardized score with a mean of 50 and a standard deviation of 10. The \[PROMIS\] Cancer Fatigue Short Form \[SF\] 7a T-Scores range from 29.4 to 83.2, with higher scores indicating more fatigue. Negative changes from baseline indicate improvement.
Time frame: Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization; participants who have both baseline and post-baseline values are included in the analysis at each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 27, Day 1 | 3.4 T-score | Standard Deviation 8.19 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 15, Day 1 | 1.5 T-score | Standard Deviation 8.84 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 29, Day 1 | 3.9 T-score | Standard Deviation 8.07 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 17, Day 1 | 1.2 T-score | Standard Deviation 8.11 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 31, Day 1 | 2.8 T-score | Standard Deviation 8.43 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 7, Day 1 | 3.2 T-score | Standard Deviation 9.28 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 33, Day 1 | 2.0 T-score | Standard Deviation 8.93 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 19, Day 1 | 0.7 T-score | Standard Deviation 8.52 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 35, Day 1 | 3.4 T-score | Standard Deviation 9.27 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 11, Day 1 | 0.6 T-score | Standard Deviation 8.54 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 37, Day 1 | 4.1 T-score | Standard Deviation 9.72 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 21, Day 1 | 1.6 T-score | Standard Deviation 8.58 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 39, Day 1 | 3.6 T-score | Standard Deviation 8.12 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 5, Day 1 | 3.3 T-score | Standard Deviation 9.25 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 41, Day 1 | 3.3 T-score | Standard Deviation 8.69 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 23, Day 1 | 2.0 T-score | Standard Deviation 8.08 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 43, Day 1 | 5.3 T-score | Standard Deviation 9.28 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 13, Day 1 | 1.8 T-score | Standard Deviation 8.03 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 45, Day 1 | -0.3 T-score | Standard Deviation 7.99 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 25, Day 1 | 2.0 T-score | Standard Deviation 8.59 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 47, Day 1 | -2.5 T-score | Standard Deviation 6.3 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 9, Day 1 | 2.3 T-score | Standard Deviation 8.9 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Final visit | 5.0 T-score | Standard Deviation 10.95 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 3, Day 1 | 2.2 T-score | Standard Deviation 9.54 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Final visit | 2.9 T-score | Standard Deviation 9.96 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 15, Day 1 | 2.1 T-score | Standard Deviation 7.66 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 3, Day 1 | 1.8 T-score | Standard Deviation 8.12 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 5, Day 1 | 2.4 T-score | Standard Deviation 10.34 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 7, Day 1 | 2.6 T-score | Standard Deviation 9.7 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 9, Day 1 | 2.6 T-score | Standard Deviation 8.67 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 11, Day 1 | 3.1 T-score | Standard Deviation 8.98 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 13, Day 1 | 2.3 T-score | Standard Deviation 6.97 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 17, Day 1 | 2.6 T-score | Standard Deviation 8.05 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 19, Day 1 | 0.9 T-score | Standard Deviation 9.32 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 21, Day 1 | 1.2 T-score | Standard Deviation 7.66 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 23, Day 1 | 1.5 T-score | Standard Deviation 8.83 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 25, Day 1 | -0.1 T-score | Standard Deviation 8.73 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 27, Day 1 | -0.1 T-score | Standard Deviation 9.59 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 29, Day 1 | 0.8 T-score | Standard Deviation 8.51 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 31, Day 1 | -0.3 T-score | Standard Deviation 9.15 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 33, Day 1 | 3.7 T-score | Standard Deviation 9.17 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 35, Day 1 | 1.1 T-score | Standard Deviation 7.22 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 37, Day 1 | -3.0 T-score | Standard Deviation 11.72 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 39, Day 1 | 4.1 T-score | Standard Deviation 2.82 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 41, Day 1 | -0.7 T-score | Standard Deviation 6.9 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 43, Day 1 | 4.4 T-score | Standard Deviation 1.91 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 45, Day 1 | 1.8 T-score | Standard Deviation 0.28 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] Score | Cycle 47, Day 1 | 0.0 T-score | — |
Secondary
Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
The QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including five functional scales (physical, role, emotional, social, and cognitive), three symptom scales (fatigue, nausea and vomiting, and pain), a global health status/quality of life scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). For the Physical Functioning scale, participants rate five items on a four-point scale, with 1 as not at all and 4 as very much. The Physical Functioning Scale scores range from 0 to 100 and were calculated per the EORTC QLQ-C30 Scoring Manual (3rd edition), version 3.0. A high scale score represents high/healthy level of functioning. Positive changes from baseline indicate improvement.
Time frame: Baseline; Cycle 3 (Cycles 1 - 8 are 21 days, Cycles 9 and beyond are 35 days) through Cycle 47, collected on Day 1 of every other cycle and at the Treatment Completion Visit (TCV) while participant is on treatment
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization; participants who have both baseline and post-baseline values are included in the analysis at each visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 15, Day 1 | -2.3 units on a scale | Standard Deviation 18.72 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 5, Day 1 | -3.9 units on a scale | Standard Deviation 18.38 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 7, Day 1 | -6.1 units on a scale | Standard Deviation 20.19 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 9, Day 1 | -3.5 units on a scale | Standard Deviation 19.54 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 11, Day 1 | -1.5 units on a scale | Standard Deviation 15.92 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 13, Day 1 | -3.2 units on a scale | Standard Deviation 16.57 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 3, Day 1 | -5.0 units on a scale | Standard Deviation 18.22 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 17, Day 1 | -1.8 units on a scale | Standard Deviation 16.23 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 19, Day 1 | -2.5 units on a scale | Standard Deviation 19.3 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 21, Day 1 | -1.5 units on a scale | Standard Deviation 17.81 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 23, Day 1 | -3.4 units on a scale | Standard Deviation 20.32 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 25, Day 1 | -3.8 units on a scale | Standard Deviation 17.28 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 27, Day 1 | -8.6 units on a scale | Standard Deviation 21.69 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 29, Day 1 | -8.7 units on a scale | Standard Deviation 21.25 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 31, Day 1 | -2.8 units on a scale | Standard Deviation 17.98 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 33, Day 1 | -4.0 units on a scale | Standard Deviation 22.76 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 35, Day 1 | -7.0 units on a scale | Standard Deviation 16.64 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 37, Day 1 | -7.5 units on a scale | Standard Deviation 22.49 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 39, Day 1 | -10.1 units on a scale | Standard Deviation 18.8 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 41, Day 1 | -13.0 units on a scale | Standard Deviation 25.65 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 43, Day 1 | -7.8 units on a scale | Standard Deviation 23.12 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 45, Day 1 | -1.3 units on a scale | Standard Deviation 10.33 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Final visit | -11.8 units on a scale | Standard Deviation 22.85 |
| Venetoclax + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 47, Day 1 | 0.0 units on a scale | Standard Deviation 14.4 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Final visit | -10.0 units on a scale | Standard Deviation 21.52 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 3, Day 1 | -4.6 units on a scale | Standard Deviation 19.5 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 27, Day 1 | -3.3 units on a scale | Standard Deviation 18.44 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 5, Day 1 | -7.8 units on a scale | Standard Deviation 21.5 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 39, Day 1 | 8.9 units on a scale | Standard Deviation 10.18 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 7, Day 1 | -8.6 units on a scale | Standard Deviation 19.76 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 29, Day 1 | -4.0 units on a scale | Standard Deviation 19.81 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 9, Day 1 | -8.0 units on a scale | Standard Deviation 20.01 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 45, Day 1 | 13.3 units on a scale | Standard Deviation 18.86 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 11, Day 1 | -7.5 units on a scale | Standard Deviation 18.46 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 31, Day 1 | 2.2 units on a scale | Standard Deviation 18.56 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 13, Day 1 | -8.8 units on a scale | Standard Deviation 22.85 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 41, Day 1 | 13.3 units on a scale | Standard Deviation 23.09 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 15, Day 1 | -7.3 units on a scale | Standard Deviation 22.27 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 33, Day 1 | -4.8 units on a scale | Standard Deviation 23.64 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 17, Day 1 | -8.6 units on a scale | Standard Deviation 19.9 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 47, Day 1 | 0.0 units on a scale | — |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 19, Day 1 | -7.0 units on a scale | Standard Deviation 19.35 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 35, Day 1 | 4.4 units on a scale | Standard Deviation 18.7 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 21, Day 1 | -8.5 units on a scale | Standard Deviation 20.43 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 43, Day 1 | 13.3 units on a scale | Standard Deviation 18.86 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 23, Day 1 | -7.5 units on a scale | Standard Deviation 20.53 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 37, Day 1 | 15.0 units on a scale | Standard Deviation 14.78 |
| Placebo + Bortezomib and Dexamethasone | Mean Change From Baseline in Physical Functioning Scale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Cycle 25, Day 1 | 0.5 units on a scale | Standard Deviation 23.95 |
Secondary
Minimal Residual Disease (MRD) Negativity Rate
MRD negativity rate is defined as the percentage of participants who have negative MRD by bone marrow aspirate at any time point after randomization and before progression or starting subsequent therapy. MRD negativity was defined at 10\^-5 threshold (less than one residual myeloma cell per 10\^5 total nucleated cells) as measured by centralized testing of bone marrow aspirate by Next Generation Sequencing (NGS). MRD positive participants include those of which all tested samples were found to be MRD positive or indeterminate. Participants with missing or unevaluable MRD status were considered as MRD positive.
Time frame: Assessed at Screening; to confirm a stringent Complete Response (sCR) or Complete Response (CR); at 6 months and 12 months post-confirmed CR/sCR
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Minimal Residual Disease (MRD) Negativity Rate | 15.5 percentage of participants |
| Placebo + Bortezomib and Dexamethasone | Minimal Residual Disease (MRD) Negativity Rate | 2.1 percentage of participants |
Comparison: Stratified Analysis; Stratification factors: Prior exposure to proteasome inhibitors (naïve versus sensitive), and number of prior lines of therapy (1 versus 2 or 3)p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Overall Response Rate (ORR)
Overall response rate is defined as the percentage of participants with documented best overall response of Partial Response (PR) or better (PR, Very good partial response \[VGPR\], Complete response \[CR\], or Stringent complete response \[sCR\]) per International Myeloma Working Group (IMWG) criteria as determined by an Independent Review Committee (IRC).
Time frame: Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Overall Response Rate (ORR) | 81.4 percentage of participants |
| Placebo + Bortezomib and Dexamethasone | Overall Response Rate (ORR) | 69.1 percentage of participants |
Comparison: Stratified Analysis; Stratification factors: Prior exposure to proteasome inhibitors (naïve versus sensitive), and number of prior lines of therapy (1 versus 2 or 3)p-value: =0.019Cochran-Mantel-Haenszel
Secondary
Overall Survival (OS).
OS is defined as the number of days from the date of randomization to the date of death due to any cause. All events of death were to be included, regardless of whether the event occurred while the participant was still taking study drug or after the participant discontinued study drug. If a participant is not known to have died, OS was censored at the date of last contact. The distribution of OS was estimated using Kaplan-Meier methodology.
Time frame: Median duration of follow-up was 45.6 months for the venetoclax group and 45.6 months for the placebo group
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Overall Survival (OS). | NA months |
| Placebo + Bortezomib and Dexamethasone | Overall Survival (OS). | NA months |
Comparison: Stratified Analysis; Stratification factors: Prior exposure to proteasome inhibitors (naïve versus sensitive), and number of prior lines of therapy (1 versus 2 or 3)p-value: =0.38595% CI: [0.802, 1.77]Log Rank
Secondary
Progression-Free Survival (PFS) in Participants With High B-cell Lymphoma 2 (BCL-2) Expression
PFS is defined as the number of days from the date the participant was randomized to the date of the first documented progressive disease (PD) per investigator assessment or death due to any cause, whichever occurs first. PFS was analyzed by Kaplan-Meier methodology. BCL-2 expression was determined through central laboratory testing by immunohistochemistry (IHC) and based on a pre-specified scoring algorithm. High clinical score of 2+: ≥50% of tumor cells with moderate or higher cytoplasmic staining but \< 50% of tumor cells with strong staining intensity; high clinical score of 3+: ≥50% of tumor cells with strong cytoplasmic staining.
Time frame: Median duration of follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization who had high BCL-2 expression
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Progression-Free Survival (PFS) in Participants With High B-cell Lymphoma 2 (BCL-2) Expression | 23.8 months |
| Placebo + Bortezomib and Dexamethasone | Progression-Free Survival (PFS) in Participants With High B-cell Lymphoma 2 (BCL-2) Expression | 11.4 months |
Secondary
Time to Progression (TTP)
TTP is defined as the number of days from the date of randomization to the date of first documented progressive disease (PD) as determined by an Independent Review Committee (IRC) or death due to multiple myeloma, whichever occurs first. TTP was analyzed by Kaplan-Meier methodology.
Time frame: Median time on follow-up up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Time to Progression (TTP) | 25.4 months |
| Placebo + Bortezomib and Dexamethasone | Time to Progression (TTP) | 12.2 months |
Comparison: Stratified Analysis; Stratification factors: Prior exposure to proteasome inhibitors (naïve versus sensitive), and number of prior lines of therapy (1 versus 2 or 3)p-value: =0.00195% CI: [0.405, 0.805]Log Rank
Secondary
Very Good Partial Response (VGPR) or Better Response Rate
The percentage of participants with documented best overall response of Very Good Partial Response (VGPR) or better (VGPR, Complete response \[CR\], or Stringent complete response \[sCR\]) per 2016 standard International Myeloma Working Group (IMWG) criteria as determined by an Independent Review Committee (IRC) was computed.
Time frame: Response was assessed at Cycle 1, Day 1, and on Day 1 of every cycle thereafter; median time on follow-up was 28.6 months for the venetoclax group and 28.6 months for the placebo group
Population: Intent-To-Treat (ITT) analysis set: all randomized participants, analyzed by treatment group assignment given at the time of randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Venetoclax + Bortezomib and Dexamethasone | Very Good Partial Response (VGPR) or Better Response Rate | 60.3 percentage of participants |
| Placebo + Bortezomib and Dexamethasone | Very Good Partial Response (VGPR) or Better Response Rate | 38.1 percentage of participants |
Comparison: Stratified Analysis; Stratification factors: Prior exposure to proteasome inhibitors (naïve versus sensitive), and number of prior lines of therapy (1 versus 2 or 3)p-value: <0.001Cochran-Mantel-Haenszel