An Investigational Drug, Palbociclib (PD-0332991), Is Being Studied In Combination With Velcade And Dexamethasone In Patients With Multiple Myeloma. Patients Must Have Received Prior Treatment For Multiple Myeloma.

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00555906
• Collaborator: (none)
• Enrollment: 53
• Locations: 19
• Arm: 1
• Duration (Months): 62
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is a Phase 1/2 study evaluating the safety and anti-tumor activity of PD 0332991 in combination with Velcade® [bortezomib] and dexamethasone in patients who have received at least one previous treatment for multiple myeloma.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Bortezomib; Drug: Dexamethasone; Drug: PD 0332991	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Open-label Study Of The Safety And Efficacy Of Pd 0332991 In Combination With Bortezomib And Dexamethasone In Patients With Refractory Multiple Myeloma
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 1

Drug: Bortezomib; Escalating doses of bortezomib will be administered intravenously on Days 8, 11, 15 and 18 of a 28-day cycle (Schedule A) or of a 21-day cycle (Schedule B). The planned doses to be evaluated are 0.7, 1 and 1.3 mg/m2 in combination with PD 0332991 and dexamethasone.; Other Names: Velcade ; Drug: Dexamethasone; 20 mg, orally on Days 8, 11, 15 and 18 of a 28 day cycle (Schedule A) or of a 21-day cycle (Schedule B) in combination with PD 0332991 and bortezomib.; Drug: PD 0332991; Escalating doses of PD 0332991 will be administered orally on Days 1-21 of a 28-day cycle for Schedule A and on Days 1-12 of a 21-day cycle for Schedule B. The planned doses to be evaluated are 50, 75, 100 mg and 125 mg once daily in combination with bortezomib and dexamethasone.

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of PD-0332991: Phase 1 [Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B]

   MTD=highest dose level for which no more than 1 out of 6 participants experienced dose-limiting toxicity (DLT). DLT=any of the following treatment-related events: Absolute neutrophil count (ANC) less than (<)1000/microliter (mcL) (Grade 3 neutropenia) associated with documented infection/fever >=38.5degrees Celsius (C); Grade >=3 nonhematologic treatment-related toxicity, except those that were not maximally treated or considered tolerable, Grade 3 corrected QT interval (QTc) prolongation (QTc >500 millisecond [msec]) in asymptomatic participants even after repeat testing to exclude confounding factors and correction of reversible causes; Delay in the administration of Cycle 2 for more than 1 week of the planned date due to platelet count <25,000/mcL and/or ANC <500/mcL, or due to prolonged nonhematologic toxicities of Grade >=3; Inability to deliver at least 80 percent (%) of the planned PD 0332991 or bortezomib doses during Cycle 1 due to toxicity.

2. Recommended Phase II Dose (RP2D) of PD-0332991: Phase 1 [Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B]

   RP2D was determined based on the MTD, safety and tolerability profile of the study treatment.

3. Percentage of Participants With Objective Response (OR): Phase 2 [Cycle 1 Day 1 (baseline) up to end of study (up to cycle 22 for schedule B)]

   OR: confirmed stringent complete response(sCR),complete response(CR),very good partial response(VGPR) or partial response(PR) as per International Myeloma Working Group Uniform Response Criteria (IMWGURC). sCR: normal serum free light chain (FLC) ratio, absence of clonal cells in bone marrow. CR: disappearance of any soft tissue plasmacytomas, <5 percent (%) plasma cells in bone marrow, negative immunofixation on serum, urine. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis, >= 90% reduction in serum M-protein, <100 mg/24 hour (hr) urine M-protein. PR: >=50% reduction in serum M-protein, reduction in 24-hr urinary M-protein by >=90% or to <200 mg/24 hr, >=50% decrease in difference between involved and uninvolved FLC levels if serum, urine M-protein were unmeasurable, >= 50% reduction in plasma cells, provided baseline bone marrow plasma cell was >=30% if serum, urine M-protein were unmeasurable and serum free light assay was unmeasureable.

Secondary Outcome Measures

1. Percent Change From Screening in Phosphorylated Retinoblastoma (Rb), Tumor Biomarkers and Soluble Biomarkers Levels: Phase 1 [Screening, C1D1(baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)]

2. Best Overall Response: Phase 1 [Cycle 1 Day 1 (baseline), assessed on Day 1 of every cycle up to end of study (up to Cycle 22 for schedule A and schedule B)]

   Best overall response: best confirmed response on study after first study dose as per IMWGURC. sCR: normal FLC ratio, absence of clonal cells in bone marrow. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis, >=90% reduction in serum M-protein, <100 mg/24 hr urine M-protein. PR: >=50% reduction of serum M-protein, reduction in 24-hr urinary M-protein by >=90% or to <200mg/24 hr. Progressive disease (PD): >=25% increase from lowest response level in serum M-component or urine M-component, >=10% bone marrow plasma cell percentage, definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia, attributed solely to plasma cell proliferative disorder. Stable disease (SD): criteria for CR, VGPR, PR or PD not met.

3. Time to Tumor Progression (TTP): Phase 2 [Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib]

   TTP was defined as the time from first dose of study medication to first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per IMWGURC). PD: >=25% increase from lowest response level in serum M-component or urine M-component, >=10% bone marrow plasma cell percentage, definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia, attributed solely to plasma cell proliferative disorder.

4. Progression-free Survival (PFS): Phase 2 [Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib]

   PFS was the time from start of study treatment to date progressive disease was documented or death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death"). PD: >=25% increase from lowest response level in serum M-component or urine M-component, >=10% bone marrow plasma cell percentage, definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia, attributed solely to plasma cell proliferative disorder.

5. Duration of Objective Response (DR): Phase 2 [Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib]

   DR was defined as time from first documentation of objective tumor response (sCR, CR, VGPR or PR) that was subsequently confirmed to first documentation of objective tumor progression or death due to any cause since treatment started. sCR: normal FLC ratio, absence of clonal cells in bone marrow. CR: disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow, negative immunofixation on serum, urine. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis, >=90% reduction in serum M-protein, <100 mg/24hr urine M-protein. PR:>=50% reduction in serum M-protein, reduction in 24-hr urinary M-protein by >=90% or to <200 mg/24 hr. PD: >=25% increase from lowest response level in serum M-component, urine M-component, >=10% bone marrow plasma cell percentage, development of new bone lesions/soft tissue plasmacytomas/increase in size of existing bone lesions, development of hypercalcemia, attributed solely to plasma cell proliferative disorder.

6. Overall Survival (OS): Phase 2 [Cycle 1 Day 1 (baseline) up to end of study (up to Cycle 22 for schedule B), thereafter every 3 months until 1 year after the last dose of palbociclib]

   OS was defined as the time from first dose of study medication to first documentation of death due to any cause. OS was calculated as (the death date or last known alive date [if death date unavailable] minus the date of first dose of study medication plus 1) divided by 30.44.

7. Number of Participants With Adverse Events (AEs) by Severity: Phase 2 [Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib]

   An AE was any untoward medical occurrence attributed to study medication in a participant who received study medication. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Adverse events were graded according to the common terminology criteria for adverse events (CTCAE) criteria as 1=mild AE, 2=moderate AE, 3=severe AE, 4=life-threatening or disabling AE, 5=Death related to AE. The most severe grade was used in case of multiple occurrences of the same event.

8. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Medication: Phase 2 [Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib]

   An AE was any untoward medical occurrence attributed to study medication in a participant who received study medication. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication until 28 days after the last dose of study medication that were absent before treatment or that worsened relative to pretreatment state. All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study medication, which occurred during the trial. Treatment-related were adverse events (serious as well as non-serious adverse events) considered related to study medication by the investigator. Number of participants with treatment related TEAEs and all causality TEAEs were summarized.

9. Number of Participants With Laboratory Abnormalities: Phase 2 [Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib]

   Laboratory parameters included hematology (hemoglobin, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); liver function (total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein); renal function (creatinine, blood urea nitrogen, uric acid); electrolytes (sodium, potassium, chloride, bicarbonate, calcium, magnesium and phosphate); urinalysis (protein and immunology [C reactive protein]), and clinical chemistry (glucose). Total number of participants with laboratory abnormalities was reported.

10. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30): Phase 2 [C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)]

    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores for functional scales, global health status and symptom scales were calculated as an average of individual items, transformed to 0-100 scale; higher score=better level of functioning, health status or greater degree of symptoms. Score of the single items were transformed to 0-100 scale; higher score=greater degree of symptom/difficulty.

11. Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20): Phase 2 [C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)]

    The QLQ-MY20 consisted of 20 items addressing 4 domains of health-related quality of life (HRQoL) important to participants with multiple myeloma: future perspective (2 items), pain/disease symptoms (6 items), social support /body image (2 items), and treatment side-effects (10 items). All items used 4 point scale (1 'Not at all' to 4 'Very much'). Scores for HRQoL domains were calculated as an average of the individual items, transformed to 0 to 100 range. Higher scores on symptom scales (disease symptoms and side effects of treatment) indicated a higher level of symptoms/problems. Higher scores on functional scales (future perspective and body image) indicated a higher level of QoL/functioning.

12. Modified Version of Brief Pain Inventory - Short Form (m-BPI-sf) Questionnaire: Phase 2 [C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)]

    m-BPI-sf was a questionnaire designed to assess the severity of pain and the impact of pain on daily functions. m-BPI-sf contained questions that assessed pain severity (worst, least, average, right now) and pain interference (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each question was answered on a scale ranging from 0 "No pain" to 10 "Pain as bad as you can imagine". The 4 pain severity questions were averaged to derive an index of pain severity and the 7 function questions were averaged to derive an index for pain interference. Total score range for pain severity and interference indices: 0 to 10, where higher score indicated higher severity/interference.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of symptomatic multiple myeloma as defined by International Myeloma Working Group (IMWGURC).

• Phase 1: Relapsed or relapsed/refractory myeloma after at least 1 previous treatments and with a life expectancy of more than 3 months.

• Phase 2: Measurable (as defined by IMWGURC) disease after at least 1 previous treatment.

Exclusion Criteria:

• History of allogeneic stem cell transplant.

• Phase 2 only: Prior bortezomib therapy will only be allowed if there was a demonstrated positive response, and disease progression occurred off therapy.

• Must have not experienced significant blood level changes, e.g. very low platelets, while on previous bortezomib therapy

• Prior radiation therapy to > 25% of the bone marrow (whole pelvis is 25%).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern Medical Faculty Foundation	Chicago	Illinois	United States	60611
2	Northwestern Memorial Hospital/Main Labs	Chicago	Illinois	United States	60611
3	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
4	University of Kansas Cancer Center and Medical Pavilion	Westwood	Kansas	United States	66205
5	University of Maryland	Baltimore	Maryland	United States	21201
6	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
7	Washington University School of Medicine	St. Louis	Missouri	United States	63110-1093
8	Barnes-Jewish Hospital	St. Louis	Missouri	United States	63110
9	Washington University School of Medicine	St. Louis	Missouri	United States	63110
10	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
11	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
12	New York Presbyterian, Weill Cornell Medical College	New York	New York	United States	10065
13	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
14	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232
15	Hollings Cancer Center	Charleston	South Carolina	United States	29425
16	Medical University of South Carolina	Charleston	South Carolina	United States	29425
17	Vseobecna fakultni nemocnice v Praze	Praha 2		Czech Republic	12808
18	Universitaetsklinikum Heidelberg	Heidelberg		Germany	69120
19	Klinikum Johannes-Gutenberg -Universitaet, III. Medizinische Klinik und Poliklinik	Mainz		Germany	55131

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00555906
• Other Study ID Numbers: A5481004; 2010-022515-20
• First Posted: Nov 9, 2007
• Last Update Posted: Mar 19, 2015
• Last Verified: Mar 1, 2015

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Bortezomib; Palbociclib

Study Results

Participant Flow

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule A)	Palbociclib 75mg+Bortezomib+Dexamethasone(Phase1:Schedule A)	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule B)	Palbociclib 125mg+Bortezomib+Dexamethasone(Phase1:Schedule B)	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:ScheduleB)
Arm/Group Description	Palbociclib (PD 0332991) 100 milligram (mg) capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 milligram per square meter (mg/m^2) intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 75 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 125 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Period Title: Phase 1
STARTED	3	6	7	5	0
COMPLETED	0	0	0	0	0
NOT COMPLETED	3	6	7	5	0
Period Title: Phase 1
STARTED	0	0	0	0	32
Treated	0	0	0	0	30
COMPLETED	0	0	0	0	0
NOT COMPLETED	0	0	0	0	32

Baseline Characteristics

Arm/Group Title	Palbociclib + Bortezomib + Dexamethasone (Phase1:Schedule A)	Palbociclib + Bortezomib + Dexamethasone (Phase1:Schedule B)	Palbociclib + Bortezomib + Dexamethasone (Phase2:ScheduleB)	Total
Arm/Group Description	Included all participants who received palbociclib (PD 0332991) 75 mg or 100 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Included all participants who received palbociclib (PD 0332991) 100 mg or 125 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Included all participants who received palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Total of all reporting groups
Overall Participants	9	12	32	53
Age, Customized (participants) [Number]
18 to 44 years	2 22.2%	1 8.3%	0 0%	3 5.7%
45 to 64 years	4 44.4%	7 58.3%	13 40.6%	24 45.3%
Greater than or equal to (>=) 65 years	3 33.3%	4 33.3%	19 59.4%	26 49.1%
Sex: Female, Male (Count of Participants)
Female	5 55.6%	1 8.3%	17 53.1%	23 43.4%
Male	4 44.4%	11 91.7%	15 46.9%	30 56.6%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of PD-0332991: Phase 1
Description	MTD=highest dose level for which no more than 1 out of 6 participants experienced dose-limiting toxicity (DLT). DLT=any of the following treatment-related events: Absolute neutrophil count (ANC) less than (<)1000/microliter (mcL) (Grade 3 neutropenia) associated with documented infection/fever >=38.5degrees Celsius (C); Grade >=3 nonhematologic treatment-related toxicity, except those that were not maximally treated or considered tolerable, Grade 3 corrected QT interval (QTc) prolongation (QTc >500 millisecond [msec]) in asymptomatic participants even after repeat testing to exclude confounding factors and correction of reversible causes; Delay in the administration of Cycle 2 for more than 1 week of the planned date due to platelet count <25,000/mcL and/or ANC <500/mcL, or due to prolonged nonhematologic toxicities of Grade >=3; Inability to deliver at least 80 percent (%) of the planned PD 0332991 or bortezomib doses during Cycle 1 due to toxicity.
Time Frame	Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B

Outcome Measure Data

Analysis Population Description

DLT analysis set included all enrolled participants who received at least one dose of study treatment and did not have a major deviation in the first cycle.

Arm/Group Title	Palbociclib + Bortezomib + Dexamethasone (Phase1:Schedule A)	Palbociclib + Bortezomib + Dexamethasone (Phase1:ScheduleB)
Arm/Group Description	Included all participants who received palbociclib (PD 0332991) 75 mg or 100 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Included all participants who received palbociclib (PD 0332991) 100 mg or 125 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	9	12
Number [milligram (mg)]	NA	100

2. Primary Outcome

Title	Recommended Phase II Dose (RP2D) of PD-0332991: Phase 1
Description	RP2D was determined based on the MTD, safety and tolerability profile of the study treatment.
Time Frame	Day 1 up to Day 28 during Cycle 1 in schedule A, Day 1 up to Day 21 during Cycle 1 in schedule B

Outcome Measure Data

Analysis Population Description

DLT analysis set included all enrolled participants who received at least one dose of study treatment and did not have a major deviation in the first cycle.

Arm/Group Title	Palbociclib + Bortezomib + Dexamethasone (Phase1:Schedule A)	Palbociclib + Bortezomib + Dexamethasone (Phase1:ScheduleB)
Arm/Group Description	Included all participants who received palbociclib (PD 0332991) 75 mg or 100 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Included all participants who received palbociclib (PD 0332991) 100 mg or 125 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	9	12
Number [milligram (mg)]	NA	100

3. Primary Outcome

Title	Percentage of Participants With Objective Response (OR): Phase 2
Description	OR: confirmed stringent complete response(sCR),complete response(CR),very good partial response(VGPR) or partial response(PR) as per International Myeloma Working Group Uniform Response Criteria (IMWGURC). sCR: normal serum free light chain (FLC) ratio, absence of clonal cells in bone marrow. CR: disappearance of any soft tissue plasmacytomas, <5 percent (%) plasma cells in bone marrow, negative immunofixation on serum, urine. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis, >= 90% reduction in serum M-protein, <100 mg/24 hour (hr) urine M-protein. PR: >=50% reduction in serum M-protein, reduction in 24-hr urinary M-protein by >=90% or to <200 mg/24 hr, >=50% decrease in difference between involved and uninvolved FLC levels if serum, urine M-protein were unmeasurable, >= 50% reduction in plasma cells, provided baseline bone marrow plasma cell was >=30% if serum, urine M-protein were unmeasurable and serum free light assay was unmeasureable.
Time Frame	Cycle 1 Day 1 (baseline) up to end of study (up to cycle 22 for schedule B)

Outcome Measure Data

Analysis Population Description

Primary response analysis set (PRAS) included first consecutive (by first treatment day) participants in response analysis set (RAS=included all enrolled participants who received study treatment, had an adequate baseline tumor assessment and measurable disease) that were response-evaluable.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:ScheduleB)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	25
Number (95% Confidence Interval) [percentage of participants]	20 222.2%

4. Secondary Outcome

Title	Percent Change From Screening in Phosphorylated Retinoblastoma (Rb), Tumor Biomarkers and Soluble Biomarkers Levels: Phase 1
Time Frame	Screening, C1D1(baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)

Outcome Measure Data

Analysis Population Description

Results are not reported because data was present as individual participant listings but not summarized for analysis, as per change in planned analysis.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule A)	Palbociclib 75mg+Bortezomib+Dexamethasone(Phase1:Schedule A)	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule B)	Palbociclib 125mg+Bortezomib+Dexamethasone(Phase1:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 75 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 125 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	0	0	0	0

5. Secondary Outcome

Title	Best Overall Response: Phase 1
Description	Best overall response: best confirmed response on study after first study dose as per IMWGURC. sCR: normal FLC ratio, absence of clonal cells in bone marrow. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow. VGPR: serum and urine M-protein detectable by immunofixation but not on electrophoresis, >=90% reduction in serum M-protein, <100 mg/24 hr urine M-protein. PR: >=50% reduction of serum M-protein, reduction in 24-hr urinary M-protein by >=90% or to <200mg/24 hr. Progressive disease (PD): >=25% increase from lowest response level in serum M-component or urine M-component, >=10% bone marrow plasma cell percentage, definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia, attributed solely to plasma cell proliferative disorder. Stable disease (SD): criteria for CR, VGPR, PR or PD not met.
Time Frame	Cycle 1 Day 1 (baseline), assessed on Day 1 of every cycle up to end of study (up to Cycle 22 for schedule A and schedule B)

Outcome Measure Data

Analysis Population Description

RAS included all enrolled participants who received study treatment, had an adequate baseline tumor assessment and measurable disease.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule A)	Palbociclib 75mg+Bortezomib+Dexamethasone(Phase1:Schedule A)	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule B)	Palbociclib 125mg+Bortezomib+Dexamethasone(Phase1:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 75 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.	Palbociclib (PD 0332991) 125 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	1	5	7	5
Stringent Complete Response	0 0%	0 0%	0 0%	0 0%
Complete Response	0 0%	0 0%	0 0%	0 0%
Very Good Partial Response	0 0%	1 8.3%	0 0%	1 1.9%
Partial Response	0 0%	0 0%	0 0%	0 0%
Stable Disease	0 0%	1 8.3%	4 12.5%	2 3.8%
Progressive Disease	1 11.1%	3 25%	3 9.4%	1 1.9%
Indeterminate	0 0%	0 0%	0 0%	1 1.9%

6. Secondary Outcome

Title	Time to Tumor Progression (TTP): Phase 2
Description	TTP was defined as the time from first dose of study medication to first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD] per IMWGURC). PD: >=25% increase from lowest response level in serum M-component or urine M-component, >=10% bone marrow plasma cell percentage, definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia, attributed solely to plasma cell proliferative disorder.
Time Frame	Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

Outcome Measure Data

Analysis Population Description

RAS included all enrolled participants who received study treatment, had an adequate baseline tumor assessment and measurable disease.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	30
Median (95% Confidence Interval) [months]	3.9

7. Secondary Outcome

Title	Progression-free Survival (PFS): Phase 2
Description	PFS was the time from start of study treatment to date progressive disease was documented or death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death"). PD: >=25% increase from lowest response level in serum M-component or urine M-component, >=10% bone marrow plasma cell percentage, definite development of new bone lesions/soft tissue plasmacytomas/definite increase in size of existing bone lesions/soft tissue plasmacytomas, development of hypercalcemia, attributed solely to plasma cell proliferative disorder.
Time Frame	Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

Outcome Measure Data

Analysis Population Description

RAS included all enrolled participants who received study treatment, had an adequate baseline tumor assessment and measurable disease.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	30
Median (95% Confidence Interval) [months]	3.9

8. Secondary Outcome

Title	Duration of Objective Response (DR): Phase 2
Description	DR was defined as time from first documentation of objective tumor response (sCR, CR, VGPR or PR) that was subsequently confirmed to first documentation of objective tumor progression or death due to any cause since treatment started. sCR: normal FLC ratio, absence of clonal cells in bone marrow. CR: disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow, negative immunofixation on serum, urine. VGPR: serum, urine M-protein detectable by immunofixation but not on electrophoresis, >=90% reduction in serum M-protein, <100 mg/24hr urine M-protein. PR:>=50% reduction in serum M-protein, reduction in 24-hr urinary M-protein by >=90% or to <200 mg/24 hr. PD: >=25% increase from lowest response level in serum M-component, urine M-component, >=10% bone marrow plasma cell percentage, development of new bone lesions/soft tissue plasmacytomas/increase in size of existing bone lesions, development of hypercalcemia, attributed solely to plasma cell proliferative disorder.
Time Frame	Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

Outcome Measure Data

Analysis Population Description

PRAS was defined as the first consecutive (by first treatment day) participants in RAS (RAS included all enrolled participants who received study treatment, had an adequate baseline tumor assessment and measurable disease) that were response-evaluable. DR was calculated for the subgroup of PRAS participants with objective response.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	5
Median (95% Confidence Interval) [months]	4.63

9. Secondary Outcome

Title	Overall Survival (OS): Phase 2
Description	OS was defined as the time from first dose of study medication to first documentation of death due to any cause. OS was calculated as (the death date or last known alive date [if death date unavailable] minus the date of first dose of study medication plus 1) divided by 30.44.
Time Frame	Cycle 1 Day 1 (baseline) up to end of study (up to Cycle 22 for schedule B), thereafter every 3 months until 1 year after the last dose of palbociclib

Outcome Measure Data

Analysis Population Description

RAS included all enrolled participants who received study treatment, had an adequate baseline tumor assessment and measurable disease.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	30
Median (95% Confidence Interval) [months]	21.1

10. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) by Severity: Phase 2
Description	An AE was any untoward medical occurrence attributed to study medication in a participant who received study medication. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Adverse events were graded according to the common terminology criteria for adverse events (CTCAE) criteria as 1=mild AE, 2=moderate AE, 3=severe AE, 4=life-threatening or disabling AE, 5=Death related to AE. The most severe grade was used in case of multiple occurrences of the same event.
Time Frame	Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	30
Grade 2	2 22.2%
Grade 3	9 100%
Grade 4	18 200%
Grade 5	1 11.1%

11. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Relationship to Study Medication: Phase 2
Description	An AE was any untoward medical occurrence attributed to study medication in a participant who received study medication. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study medication until 28 days after the last dose of study medication that were absent before treatment or that worsened relative to pretreatment state. All causality AEs included SAEs as well as non-serious AEs, without regard to relationship to the study medication, which occurred during the trial. Treatment-related were adverse events (serious as well as non-serious adverse events) considered related to study medication by the investigator. Number of participants with treatment related TEAEs and all causality TEAEs were summarized.
Time Frame	Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

Outcome Measure Data

Analysis Population Description

SAS included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	30
All Causality	30 333.3%
Treatment Related	27 300%

12. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities: Phase 2
Description	Laboratory parameters included hematology (hemoglobin, platelets, leukocytes, total neutrophils, eosinophils, basophils, lymphocytes, monocytes); liver function (total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein); renal function (creatinine, blood urea nitrogen, uric acid); electrolytes (sodium, potassium, chloride, bicarbonate, calcium, magnesium and phosphate); urinalysis (protein and immunology [C reactive protein]), and clinical chemistry (glucose). Total number of participants with laboratory abnormalities was reported.
Time Frame	Cycle 1 Day 1 (baseline) up to 28 days after last dose of palbociclib

Outcome Measure Data

Analysis Population Description

SAS included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	30
Number [participants]	30 333.3%

13. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30): Phase 2
Description	EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea and financial difficulties). Most questions used 4 point scale (1 'Not at all' to 4 'Very much'); 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores for functional scales, global health status and symptom scales were calculated as an average of individual items, transformed to 0-100 scale; higher score=better level of functioning, health status or greater degree of symptoms. Score of the single items were transformed to 0-100 scale; higher score=greater degree of symptom/difficulty.
Time Frame	C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)

Outcome Measure Data

Analysis Population Description

Patient Reported Outcomes (PRO) analysis set included all enrolled participants who received study treatment, had a baseline PRO assessment, and completed at least 1 on-study PRO assessment. Here 'n' signifies those participants who were evaluable at specified time points for each arm, respectively.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	27
C1D1: Global Health Status (n=27)	60.80
C1D1: Physical Functioning (n=27)	64.20
C1D1: Role Functioning (n=27)	59.88
C1D1: Emotional Functioning (n=27)	70.37
C1D1: Cognitive Functioning (n=27)	72.22
C1D1: Social Functioning (n=27)	69.14
C1D1: Fatigue (n=27)	29.63
C1D1: Nausea and Vomiting (n=27)	6.79
C1D1: Pain (n=27)	35.80
C1D1: Dyspnea (n=27)	32.10
C1D1: Insomnia (n=27)	43.21
C1D1: Appetite Loss (n=27)	20.99
C1D1: Constipation (n=27)	27.16
C1D1: Diarrhea (n=27)	11.11
C1D1: Financial Problems (n=26)	33.33
C1D8: Global Health Status (n=26)	60.58
C1D8: Physical Functioning (n=26)	67.18
C1D8: Role Functioning (n=26)	59.62
C1D8: Emotional Functioning (n=26)	72.76
C1D8: Cognitive Functioning (n=26)	69.87
C1D8: Social Functioning (n=26)	70.51
C1D8: Fatigue (n=26)	27.24
C1D8: Nausea and Vomiting (n=26)	12.82
C1D8: Pain (n=26)	42.31
C1D8: Dyspnea (n=26)	30.77
C1D8: Insomnia (n=26)	43.59
C1D8: Appetite Loss (n=26)	24.36
C1D8: Constipation (n=26)	34.62
C1D8: Diarrhea (n=26)	15.38
C1D8: Financial Problems	28.20
C1D15: Global Health Status	55.33
C1D15: Physical Functioning (n=25)	62.93
C1D15: Role Functioning (n=25)	52.67
C1D15: Emotional Functioning (n=25)	67.00
C1D15: Cognitive Functioning (n=25)	68.00
C1D15: Social Functioning (n=25)	64.00
C1D15: Fatigue (n=25)	33.00
C1D15: Nausea and Vomiting (n=25)	20.67
C1D15: Pain (n=25)	45.33
C1D15: Dyspnea (n=25)	42.67
C1D15: Insomnia (n=25)	40.00
C1D15: Appetite Loss (n=25)	29.33
C1D15: Constipation (n=25)	32.00
C1D15: Diarrhea (n=25)	20.00
C1D15: Financial Problems (n=25)	29.33
C2D1: Global Health Status (n=25)	52.33
C2D1: Physical Functioning (n=25)	63.73
C2D1: Role Functioning (n=25)	60.67
C2D1: Emotional Functioning (n=25)	65.67
C2D1: Cognitive Functioning (n=25)	72.00
C2D1: Social Functioning (n=25)	64.67
C2D1: Fatigue (n=25)	34.33
C2D1: Nausea and Vomiting (n=25)	12.67
C2D1: Pain (n=25)	43.33
C2D1: Dyspnea (n=25)	33.33
C2D1: Insomnia (n=25)	40.00
C2D1: Appetite Loss (n=25)	22.67
C2D1: Constipation (n=25)	21.33
C2D1: Diarrhea (n=25)	6.67
C2D1: Financial Problems (n=25)	29.33
C3D1: Global Health Status (n=25)	56.82
C3D1: Physical Functioning (n=25)	68.18
C3D1: Role Functioning (n=22)	62.88
C3D1: Emotional Functioning (n=22)	68.56
C3D1: Cognitive Functioning (n=22)	71.97
C3D1: Social Functioning (n=22)	70.45
C3D1: Fatigue (n=22)	31.44
C3D1: Nausea and Vomiting (n=22)	14.39
C3D1: Pain (n=22)	30.30
C3D1: Dyspnea (n=22)	36.36
C3D1: Insomnia (n=22)	36.36
C3D1: Appetite Loss (n=22)	22.73
C3D1: Constipation (n=22)	36.36
C3D1: Diarrhea (n=22)	6.06
C3D1: Financial Problems (n=22)	34.85
C4D1: Global Health Status (n=18)	59.72
C4D1: Physical Functioning (n=18)	63.15
C4D1: Role Functioning (n=18)	60.19
C4D1: Emotional Functioning (n=18)	67.13
C4D1: Cognitive Functioning (n=18)	71.30
C4D1: Social Functioning (n=18)	64.81
C4D1: Fatigue (n=18)	32.87
C4D1: Nausea and Vomiting (n=18)	9.26
C4D1: Pain (n=18)	30.56
C4D1: Dyspnea (n=18)	37.04
C4D1: Insomnia (n=18)	35.19
C4D1: Appetite Loss (n=18)	20.37
C4D1: Constipation (n=18)	33.33
C4D1: Diarrhea (n=18)	5.56
C4D1: Financial Problems (n=18)	33.33
C5D1:Global Health Status (n=17)	52.45
C5D1: Physical Functioning (n=17)	58.04
C5D1: Role Functioning (n=17)	56.86
C5D1: Emotional Functioning (n=17)	65.20
C5D1: Cognitive Functioning (n=17)	67.65
C5D1: Social Functioning (n=17)	59.80
C5D1: Fatigue (n=17)	34.80
C5D1: Nausea and Vomiting (n=17)	11.76
C5D1: Pain (n=17)	31.37
C5D1: Dyspnea (n=17)	45.10
C5D1: Insomnia (n=17)	27.45
C5D1: Appetite Loss (n=17)	17.65
C5D1: Constipation (n=17)	35.29
C5D1: Diarrhea (n=17)	9.80
C5D1: Financial Problems (n=17)	27.45
C6D1: Global Health Status (n=15)	61.11
C6D1: Physical Functioning (n=15)	65.78
C6D1: Role Functioning (n=15)	61.11
C6D1: Emotional Functioning (n=15)	73.89
C6D1: Cognitive Functioning (n=15)	72.22
C6D1: Social Functioning (n=15)	71.11
C6D1: Fatigue (n=15)	26.11
C6D1: Nausea and Vomiting (n=15)	7.78
C6D1: Pain (n=15)	27.78
C6D1: Dyspnea (n=15)	31.11
C6D1: Insomnia (n=15)	31.11
C6D1: Appetite Loss (n=15)	11.11
C6D1: Constipation (n=15)	28.89
C6D1: Diarrhea (n=15)	4.44
C6D1: Financial Problems (n=15)	26.67
C7D1: Global Health Status (n=11)	53.79
C7D1: Physical Functioning (n=11)	56.36
C7D1: Role Functioning (n=11)	51.52
C7D1: Emotional Functioning (n=11)	66.67
C7D1: Cognitive Functioning (n=11)	74.24
C7D1: Social Functioning (n=11)	68.18
C7D1: Fatigue (n=11)	33.33
C7D1: Nausea and Vomiting (n=11)	12.12
C7D1: Pain (n=11)	37.88
C7D1: Dyspnea (n=11)	20.00
C7D1: Insomnia (n=11)	30.30
C7D1: Appetite Loss (n=11)	6.06
C7D1: Constipation (n=11)	27.27
C7D1: Diarrhea (n=11)	12.12
C7D1: Financial Problems (n=11)	27.27
C8D1: Global Health Status (n=10)	62.50
C8D1: Physical Functioning (n=10)	56.00
C8D1: Role Functioning (n=10)	58.33
C8D1: Emotional Functioning (n=10)	78.33
C8D1: Cognitive Functioning (n=10)	78.33
C8D1: Social Functioning (n=10)	73.33
C8D1: Fatigue (n=10)	21.67
C8D1: Nausea and Vomiting (n=10)	5.00
C8D1: Pain (n=10)	31.67
C8D1: Dyspnea (n=10)	30.00
C8D1: Insomnia (n=10)	36.67
C8D1: Appetite Loss (n=10)	10.00
C8D1: Constipation (n=10)	20.00
C8D1: Diarrhea (n=10)	0.00
C8D1: Financial Problems (n=10)	40.00
C9D1: Global Health Status (n=9)	56.48
C9D1: Physical Functioning (n=9)	57.78
C9D1: Role Functioning (n=9)	68.52
C9D1: Emotional Functioning (n=9)	75.00
C9D1: Cognitive Functioning (n=9)	72.22
C9D1: Social Functioning (n=9)	74.07
C9D1: Fatigue (n=9)	25.00
C9D1: Nausea and Vomiting (n=9)	5.56
C9D1: Pain (n=9)	25.92
C9D1: Dyspnea (n=9)	33.33
C9D1: Insomnia (n=9)	40.74
C9D1: Appetite Loss (n=9)	11.11
C9D1: Constipation (n=9)	18.52
C9D1: Diarrhea (n=9)	7.41
C9D1: Financial Problems (n=9)	40.74
C10D1: Global Health Status (n=6)	52.78
C10D1: Physical Functioning (n=6)	52.22
C10D1: Role Functioning (n=6)	50.00
C10D1: Emotional Functioning (n=6)	70.83
C10D1: Cognitive Functioning (n=6)	75.00
C10D1: Social Functioning (n=6)	83.33
C10D1: Fatigue (n=6)	29.17
C10D1: Nausea and Vomiting (n=6)	2.78
C10D1: Pain (n=6)	33.33
C10D1: Dyspnea (n=6)	33.33
C10D1: Insomnia (n=6)	44.45
C10D1: Appetite Loss (n=6)	16.67
C10D1: Constipation (n=6)	16.67
C10D1: Diarrhea (n=6)	0.00
C10D1: Financial Problems (n=6)	38.89
C11D1: Global Health Status (n=5)	61.67
C11D1: Physical Functioning (n=5)	54.67
C11D1: Role Functioning (n=5)	53.33
C11D1: Emotional Functioning (n=5)	65.00
C11D1: Cognitive Functioning (n=5)	73.33
C11D1: Social Functioning (n=5)	66.66
C11D1: Fatigue (n=5)	35.00
C11D1: Nausea and Vomiting (n=5)	6.67
C11D1: Pain (n=5)	30.00
C11D1: Dyspnea (n=5)	20.00
C11D1: Insomnia (n=5)	40.00
C11D1: Appetite Loss (n=5)	13.33
C11D1: Constipation (n=5)	13.33
C11D1: Diarrhea (n=5)	6.67
C11D1: Financial Problems (n=5)	26.67
C12D1: Global Health Status (n=15)	45.00
C12D1: Physical Functioning (n=15)	52.00
C12D1: Role Functioning (n=15)	43.33
C12D1: Emotional Functioning (n=15)	63.33
C12D1: Cognitive Functioning (n=15)	70.00
C12D1: Social Functioning (n=15)	50.00
C12D1: Fatigue (n=15)	36.67
C12D1: Nausea and Vomiting (n=15)	6.67
C12D1: Pain (n=15)	43.33
C12D1: Dyspnea (n=15)	40.00
C12D1: Insomnia (n=15)	33.33
C12D1: Appetite Loss (n=15)	26.67
C12D1: Constipation (n=15)	6.67
C12D1: Diarrhea (n=15)	13.33
C12D1: Financial Problems (n=15)	46.67
C13D1: Global Health Status (n=6)	54.17
C13D1: Physical Functioning (n=6)	53.34
C13D1: Role Functioning (n=6)	55.56
C13D1: Emotional Functioning (n=6)	69.44
C13D1: Cognitive Functioning (n=6)	69.44
C13D1: Social Functioning (n=6)	61.11
C13D1: Fatigue (n=6)	30.56
C13D1: Nausea and Vomiting (n=6)	5.56
C13D1: Pain (n=6)	27.78
C13D1: Dyspnea (n=6)	22.22
C13D1: Insomnia (n=6)	27.78
C13D1: Appetite Loss (n=6)	16.67
C13D1: Constipation (n=6)	16.67
C13D1: Diarrhea (n=6)	22.22
C13D1: Financial Problems (n=6)	38.89
C14D1: Global Health Status (n=6)	61.11
C14D1: Physical Functioning (n=6)	54.45
C14D1: Role Functioning (n=6)	50.00
C14D1: Emotional Functioning (n=6)	73.61
C14D1: Cognitive Functioning (n=6)	83.33
C14D1: Social Functioning (n=6)	69.45
C14D1: Fatigue (n=6)	26.39
C14D1: Nausea and Vomiting (n=6)	2.78
C14D1: Pain (n=6)	33.33
C14D1: Dyspnea (n=6)	22.22
C14D1: Insomnia (n=6)	22.22
C14D1: Appetite Loss (n=6)	0.00
C14D1: Constipation (n=6)	16.67
C14D1: Diarrhea (n=6)	5.56
C14D1: Financial Problems (n=6)	33.33
C15D1: Global Health Status (n=6)	66.67
C15D1: Physical Functioning (n=6)	52.23
C15D1: Role Functioning (n=6)	61.11
C15D1: Emotional Functioning (n=6)	61.11
C15D1: Cognitive Functioning (n=6)	72.22
C15D1: Social Functioning (n=6)	66.67
C15D1: Fatigue (n=6)	22.22
C15D1: Nausea and Vomiting (n=6)	2.78
C15D1: Pain (n=6)	27.78
C15D1: Dyspnea (n=6)	27.78
C15D1: Insomnia (n=6)	22.22
C15D1: Appetite Loss (n=6)	5.56
C15D1: Constipation (n=6)	16.67
C15D1: Diarrhea (n=6)	5.56
C15D1: Financial Problems (n=6)	44.45
C16D1: Global Health Status (n=6)	52.78
C16D1: Physical Functioning (n=6)	55.56
C16D1: Role Functioning (n=6)	50.00
C16D1: Emotional Functioning (n=6)	76.39
C16D1: Cognitive Functioning (n=6)	77.78
C16D1: Social Functioning (n=6)	69.44
C16D1: Fatigue (n=6)	23.61
C16D1: Nausea and Vomiting (n=6)	0.00
C16D1: Pain (n=6)	33.33
C16D1: Dyspnea (n=6)	27.78
C16D1: Insomnia (n=6)	27.78
C16D1: Appetite Loss (n=6)	5.56
C16D1: Constipation (n=6)	11.11
C16D1: Diarrhea (n=6)	22.22
C16D1: Financial Problems (n=6)	44.45
C17D1: Global Health Status (n=6)	55.56
C17D1: Physical Functioning (n=6)	51.11
C17D1: Role Functioning (n=6)	58.34
C17D1: Emotional Functioning (n=6)	73.61
C17D1: Cognitive Functioning (n=6)	72.22
C17D1: Social Functioning (n=6)	72.22
C17D1: Fatigue (n=6)	26.39
C17D1: Nausea and Vomiting (n=6)	2.78
C17D1: Pain (n=6)	30.56
C17D1: Dyspnea (n=6)	22.22
C17D1: Insomnia (n=6)	50.00
C17D1: Appetite Loss (n=6)	5.56
C17D1: Constipation (n=6)	22.22
C17D1: Diarrhea (n=6)	5.56
C17D1: Financial Problems (n=6)	44.45
C18D1: Global Health Status (n=6)	61.11
C18D1: Physical Functioning (n=6)	48.89
C18D1: Role Functioning (n=6)	50.00
C18D1: Emotional Functioning (n=6)	70.83
C18D1: Cognitive Functioning (n=6)	61.11
C18D1: Social Functioning (n=6)	63.89
C18D1: Fatigue (n=6)	29.17
C18D1: Nausea and Vomiting (n=6)	8.33
C18D1: Pain (n=6)	61.11
C18D1: Dyspnea (n=6)	33.33
C18D1: Insomnia (n=6)	33.33
C18D1: Appetite Loss (n=6)	22.22
C18D1: Constipation (n=6)	22.22
C18D1: Diarrhea (n=6)	5.56
C18D1: Financial Problems (n=6)	44.44
C19D1: Global Health Status (n=4)	45.83
C19D1: Physical Functioning (n=4)	45.00
C19D1: Role Functioning (n=4)	37.50
C19D1: Emotional Functioning (n=4)	66.67
C19D1: Cognitive Functioning (n=4)	45.83
C19D1: Social Functioning (n=4)	50.00
C19D1: Fatigue (n=4)	33.33
C19D1: Nausea and Vomiting (n=4)	12.50
C19D1: Pain (n=4)	58.33
C19D1: Dyspnea (n=4)	25.00
C19D1: Insomnia (n=4)	41.67
C19D1: Appetite Loss (n=4)	25.00
C19D1: Constipation (n=4)	50.00
C19D1: Diarrhea (n=4)	0.00
C19D1: Financial Problems (n=4)	41.67
C20D1: Global Health Status (n=2)	37.50
C20D1: Physical Functioning (n=2)	46.67
C20D1: Role Functioning (n=2)	33.33
C20D1: Emotional Functioning (n=2)	33.33
C20D1: Cognitive Functioning (n=2)	16.67
C20D1: Social Functioning (n=2)	41.67
C20D1: Fatigue (n=2)	66.67
C20D1: Nausea and Vomiting (n=2)	16.67
C20D1: Pain (n=2)	66.67
C20D1: Dyspnea (n=2)	33.34
C20D1: Insomnia (n=2)	50.00
C20D1: Appetite Loss (n=2)	33.33
C20D1: Constipation (n=2)	16.67
C20D1: Diarrhea (n=2)	16.67
C20D1: Financial Problems (n=2)	83.34
C21D1: Global Health Status (n=1)	41.67
C21D1: Physical Functioning (n=1)	53.33
C21D1: Role Functioning (n=1)	50.00
C21D1: Emotional Functioning (n=1)	66.67
C21D1: Cognitive Functioning (n=1)	0.00
C21D1: Social Functioning (n=1)	33.33
C21D1: Fatigue (n=1)	33.33
C21D1: Nausea and Vomiting (n=1)	33.33
C21D1: Pain (n=1)	66.67
C21D1: Dyspnea (n=1)	0.00
C21D1: Insomnia (n=1)	66.67
C21D1: Appetite Loss (n=1)	33.33
C21D1: Constipation (n=1)	0.00
C21D1: Diarrhea (n=1)	0.00
C21D1: Financial Problems (n=1)	100.00
C22D1: Global Health Status (n=1)	16.67
C22D1: Physical Functioning (n=1)	53.33
C22D1: Role Functioning (n=1)	50.00
C22D1: Emotional Functioning (n=1)	83.33
C22D1: Cognitive Functioning (n=1)	33.33
C22D1: Social Functioning (n=1)	33.33
C22D1: Fatigue (n=1)	16.67
C22D1: Nausea and Vomiting (n=1)	33.33
C22D1: Pain (n=1)	83.33
C22D1: Dyspnea (n=1)	0.00
C22D1: Insomnia (n=1)	33.33
C22D1: Appetite Loss (n=1)	0.00
C22D1: Constipation (n=1)	0.00
C22D1: Diarrhea (n=1)	0.00
C22D1: Financial Problems (n=1)	100.00
End of treatment: Global health status (n=17)	49.02
End of Treatment: Physical Functioning (n=17)	56.08
End of Treatment: Role Functioning (n=17)	56.86
End of Treatment: Emotional Functioning (n=17)	62.26
End of Treatment: Cognitive Functioning (n=17)	62.75
End of Treatment: Social Functioning (n=17)	65.69
End of Treatment: Fatigue (n=17)	37.74
End of Treatment: Nausea and Vomiting (n=17)	16.67
End of Treatment: Pain (n=17)	43.14
End of Treatment: Dyspnea (n=17)	41.18
End of Treatment: Insomnia (n=17)	49.02
End of Treatment: Appetite Loss (n=17)	25.49
End of Treatment: Constipation (n=17)	43.14
End of Treatment: Diarrhea (n=17)	5.88
End of Treatment: Financial Problems (n=17)	45.10

14. Secondary Outcome

Title	Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20): Phase 2
Description	The QLQ-MY20 consisted of 20 items addressing 4 domains of health-related quality of life (HRQoL) important to participants with multiple myeloma: future perspective (2 items), pain/disease symptoms (6 items), social support /body image (2 items), and treatment side-effects (10 items). All items used 4 point scale (1 'Not at all' to 4 'Very much'). Scores for HRQoL domains were calculated as an average of the individual items, transformed to 0 to 100 range. Higher scores on symptom scales (disease symptoms and side effects of treatment) indicated a higher level of symptoms/problems. Higher scores on functional scales (future perspective and body image) indicated a higher level of QoL/functioning.
Time Frame	C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)

Outcome Measure Data

Analysis Population Description

PRO analysis set included all enrolled participants who received study treatment, had a baseline PRO assessment, and completed at least 1 on-study PRO assessment. Here 'n' signifies those participants who were evaluable at spefied time points for each arm, respectively.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	27
C1D1: Disease Symptoms (n=27)	35.68
C1D1: Side Effects of Treatment (n=27)	25.61
C1D1: Future Perspective (n=27)	46.50
C1D1: Body Image (n=27)	24.69
C1D8: Disease Symptoms (n=25)	35.51
C1D8: Side Effects of Treatment (n=25)	23.90
C1D8: Future Perspective (n=25)	44.44
C1D8: Body Image (n=25)	13.33
C1D15: Disease Symptoms (n=25)	32.31
C1D15: Side Effects of Treatment (n=25)	26.89
C1D15: Future Perspective (n=25)	48.89
C1D15: Body Image (n=25)	28.00
C2D1: Disease Symptoms (n=25)	29.82
C2D1: Side Effects of Treatment (n=25)	24.73
C2D1: Future Perspective (n=25)	46.22
C2D1: Body Image (n=25)	17.33
C3D1: Disease Symptoms (n=21)	25.13
C3D1: Side Effects of Treatment (n=21)	25.01
C3D1: Future Perspective (n=21)	44.44
C3D1: Body Image (n=21)	20.63
C4D1: Disease Symptoms (n=18)	28.71
C4D1: Side Effects of Treatment (n=18)	26.64
C4D1: Future Perspective (n=18)	44.45
C4D1: Body Image (n=18)	25.93
C5D1: Disease Symptoms (n=17)	27.78
C5D1: Side Effects of Treatment (n=17)	27.52
C5D1: Future Perspective (n=17)	45.75
C5D1: Body Image (n=17)	25.49
C6D1: Disease Symptoms (n=15)	24.08
C6D1: Side Effects of Treatment (n=15)	25.04
C6D1: Future Perspective (n=15)	40.74
C6D1: Body Image (n=15)	20.00
C7D1: Disease Symptoms (n=11)	25.96
C7D1: Side Effects of Treatment (n=11)	26.77
C7D1: Future Perspective (n=11)	44.44
C7D1: Body Image (n=11)	30.30
C8D1: Disease Symptoms (n=10)	18.56
C8D1: Side Effects of Treatment (n=10)	26.41
C8D1: Future Perspective (n=10)	35.56
C8D1: Body Image (n=10)	30.00
C9D1: Disease Symptoms (n=9)	19.14
C9D1: Side Effects of Treatment (n=9)	19.75
C9D1: Future Perspective (n=9)	39.51
C9D1: Body Image (n=9)	25.93
C10D1: Disease Symptoms (n=6)	25.93
C10D1: Side Effects of Treatment (n=6)	18.83
C10D1: Future Perspective (n=6)	33.33
C10D1: Body Image (n=6)	16.67
C11D1: Disease Symptoms (n=6)	18.52
C11D1: Side Effects of Treatment (n=6)	18.52
C11D1: Future Perspective (n=6)	38.89
C11D1: Body Image (n=6)	22.22
C12D1: Disease Symptoms (n=5)	28.89
C12D1: Side Effects of Treatment (n=5)	24.30
C12D1: Future Perspective (n=5)	53.33
C12D1: Body Image (n=5)	40.00
C13D1: Disease Symptoms (n=6)	25.00
C13D1: Side Effects of Treatment (n=6)	18.70
C13D1: Future Perspective (n=6)	37.04
C13D1: Body Image (n=6)	33.33
C14D1: Disease Symptoms (n=6)	19.45
C14D1: Side Effects of Treatment (n=6)	18.64
C14D1: Future Perspective (n=6)	35.19
C14D1: Body Image (n=6)	16.67
C15D1: Disease Symptoms (n=6)	23.15
C15D1: Side Effects of Treatment (n=6)	18.09
C15D1: Future Perspective (n=6)	38.89
C15D1: Body Image (n=6)	16.67
C16D1: Disease Symptoms (n=6)	27.78
C16D1: Side Effects of Treatment (n=6)	16.91
C16D1: Future Perspective (n=6)	37.04
C16D1: Body Image (n=6)	22.22
C17D1: Disease Symptoms (n=6)	24.07
C17D1: Side Effects of Treatment (n=6)	19.26
C17D1: Future Perspective (n=6)	38.89
C17D1: Body Image (n=6)	22.22
C18D1: Disease Symptoms (n=6)	41.85
C18D1: Side Effects of Treatment (n=6)	18.52
C18D1: Future Perspective (n=6)	38.89
C18D1: Body Image (n=6)	33.33
C19D1: Disease Symptoms (n=4)	43.06
C19D1: Side Effects of Treatment (n=4)	25.74
C19D1: Future Perspective (n=4)	38.89
C19D1: Body Image (n=4)	41.67
C20D1: Disease Symptoms (n=2)	44.45
C20D1: Side Effects of Treatment (n=2)	35.19
C20D1: Future Perspective (n=2)	66.67
C20D1: Body Image (n=2)	50.00
C21D1: Disease Symptoms (n=1)	77.78
C21D1: Side Effects of Treatment (n=1)	36.67
C21D1: Future Perspective (n=1)	44.44
C21D1: Body Image (n=1)	33.33
C22D1: Disease Symptoms (n=1)	61.11
C22D1: Side Effects of Treatment (n=1)	33.33
C22D1: Future Perspective (n=1)	44.44
C22D1: Body Image (n=1)	66.67
End of Treatment: Disease Symptoms (n=17)	37.58
End of Treatment: Side Effects of Treatment (n=17)	29.51
End of Treatment: Future Perspective (n=17)	46.41
End of Treatment: Body Image (n=17)	29.41

15. Secondary Outcome

Title	Modified Version of Brief Pain Inventory - Short Form (m-BPI-sf) Questionnaire: Phase 2
Description	m-BPI-sf was a questionnaire designed to assess the severity of pain and the impact of pain on daily functions. m-BPI-sf contained questions that assessed pain severity (worst, least, average, right now) and pain interference (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Each question was answered on a scale ranging from 0 "No pain" to 10 "Pain as bad as you can imagine". The 4 pain severity questions were averaged to derive an index of pain severity and the 7 function questions were averaged to derive an index for pain interference. Total score range for pain severity and interference indices: 0 to 10, where higher score indicated higher severity/interference.
Time Frame	C1D1 (baseline), C1D8, C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1, C21D1, C22D1, End of Treatment (assessment at early withdrawal occurring up to Cycle 22)

Outcome Measure Data

Analysis Population Description

The PRO analysis set included all enrolled participants who received study treatment, had a baseline PRO assessment, and completed at least 1 on-study PRO assessment.'N' signifies those participants who were evaluable for this outcome measure and 'n' signifies participants who were evaluable at specified time points for each arm, respectively.

Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:Schedule B)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
Measure Participants	26
C1D1: Pain Severity (n=26)	2.32
C1D8: Pain Severity (n=25)	2.62
C1D15: Pain Severity (n=24)	2.44
C2D1: Pain Severity (n=24)	2.30
C3D1: Pain Severity (n=21)	2.12
C4D1: Pain Severity (n=17)	2.02
C5D1: Pain Severity (n=16)	2.22
C6D1: Pain Severity (n=14)	1.66
C7D1: Pain Severity (n=10)	1.98
C8D1: Pain Severity (n=9)	2.47
C9D1: Pain Severity (n=9)	1.81
C10D1: Pain Severity (n=6)	1.08
C11D1: Pain Severity (n=5)	1.45
C12D1: Pain Severity (n=5)	1.67
C13D1: Pain Severity (n=6)	0.93
C14D1: Pain Severity (n=6)	1.42
C15D1: Pain Severity (n=6)	1.04
C16D1: Pain Severity (n=6)	1.46
C17D1: Pain Severity (n=6)	1.67
C18D1: Pain Severity (n=6)	2.88
C19D1: Pain Severity (n=4)	3.69
C20D1: Pain Severity (n=2)	3.50
C21D1: Pain Severity (n=1)	4.00
C22D1: Pain Severity (n=1)	4.50
End of Treatment: Pain Severity (n=16)	3.30
C1D1: Pain Interference (n=25)	2.53
C1D8: Pain Interference (n=25)	2.58
C1D15: Pain Interference (n=23)	3.06
C2D1: Pain Interference (n=23)	2.64
C3D1: Pain Interference (n=21)	2.34
C4D1: Pain Interference (n=17)	2.54
C5D1: Pain Interference (n=16)	2.74
C6D1: Pain Interference (n=14)	2.26
C7D1: Pain Interference (n=10)	2.94
C8D1: Pain Interference (n=9)	2.60
C9D1: Pain Interference (n=9)	2.13
C10D1: Pain Interference (n=6)	2.07
C11D1: Pain Interference (n=5)	2.40
C12D1: Pain Interference (n=5)	2.91
C13D1: Pain Interference (n=6)	1.90
C14D1: Pain Interference (n=6)	0.98
C15D1: Pain Interference (n=6)	1.31
C16D1: Pain Interference (n=6)	1.83
C17D1: Pain Interference (n=6)	1.50
C18D1: Pain Interference (n=6)	2.86
C19D1: Pain Interference (n=4)	4.07
C20D1: Pain Interference (n=2)	5.07
C21D1: Pain Interference (n=1)	2.57
C22D1: Pain Interference (n=1)	6.71
End of Treatment: Pain Interference (n=16)	3.46

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 75mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 125mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:ScheduleB)
Arm/Group Description	Palbociclib (PD 0332991) 100 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.		Palbociclib (PD 0332991) 75 mg capsule orally once daily for 21 days followed by 7 days off-treatment in a 28-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 28-day cycle (schedule A) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.		Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.		Palbociclib (PD 0332991) 125 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 1 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.		Palbociclib (PD 0332991) 100 mg capsule orally once daily for 12 days followed by 9 days off-treatment in a 21-day cycle along with bortezomib 1.0 mg/m^2 intravenous injection and dexamethasone 20 mg tablet orally 30 minutes prior to bortezomib injection on Day 8, 11, 15 and 18 of 21-day cycle (schedule B) during Phase 2 of the study. Treatment was continued until any of the following withdrawal criteria was met: disease progression (unless the investigator judged that participant could still derive clinical benefit from continuing the treatment and the risk/benefit was still favorable), unacceptable toxicities, need for surgery or radiation therapy considered due to progressive disease by investigator, investigator conclusion that it is in the participant's best interest to discontinue therapy, need for anti-cancer therapy, lost to follow-up, withdrawal from treatment, or withdrawal of consent.
All Cause Mortality
	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 75mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 125mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:ScheduleB)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 75mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 125mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:ScheduleB)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		3/6 (50%)		0/7 (0%)		5/5 (100%)		10/30 (33.3%)
Blood and lymphatic system disorders
Febrile neutropenia	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		3/30 (10%)
Thrombocytopenia	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Cardiac disorders
Atrial fibrillation	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Angina unstable	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Gastrointestinal disorders
Dysphagia	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Vomiting	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
General disorders
Pyrexia	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		2/30 (6.7%)
Asthenia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Disease progression	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Fatigue	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Immune system disorders
Hypersensitivity	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Infections and infestations
Bacteraemia	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Sepsis	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Bronchopneumonia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Pneumonia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
Investigations
Blood creatinine increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		2/5 (40%)		0/30 (0%)
Metabolism and nutrition disorders
Metabolic acidosis	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Hyperglycaemia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Bone pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Nervous system disorders
Central nervous system haemorrhage	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Psychiatric disorders
Confusional state	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Suicide attempt	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Chronic obstructive pulmonary disease	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Pneumonia aspiration	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Pneumothorax	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Vascular disorders
Deep vein thrombosis	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 75mg+Bortezomib+Dexamethasone(Phase1:Schedule A)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 125mg+Bortezomib+Dexamethasone(Phase1:Schedule B)		Palbociclib 100mg+Bortezomib+Dexamethasone(Phase2:ScheduleB)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		6/6 (100%)		7/7 (100%)		5/5 (100%)		30/30 (100%)
Blood and lymphatic system disorders
Anaemia	0/3 (0%)		2/6 (33.3%)		2/7 (28.6%)		1/5 (20%)		17/30 (56.7%)
Febrile neutropenia	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Hyperviscosity syndrome	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Leukopenia	0/3 (0%)		0/6 (0%)		2/7 (28.6%)		1/5 (20%)		5/30 (16.7%)
Lymphopenia	0/3 (0%)		0/6 (0%)		3/7 (42.9%)		2/5 (40%)		2/30 (6.7%)
Neutropenia	2/3 (66.7%)		6/6 (100%)		3/7 (42.9%)		4/5 (80%)		11/30 (36.7%)
Thrombocytopenia	3/3 (100%)		5/6 (83.3%)		5/7 (71.4%)		4/5 (80%)		23/30 (76.7%)
Haemoglobinaemia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Pancytopenia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Cardiac disorders
Angina pectoris	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Bundle branch block left	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Cyanosis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Palpitations	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Ear and labyrinth disorders
Ear pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Endocrine disorders
Hypothyroidism	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Eye disorders
Blepharitis	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Chalazion	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Conjunctivitis	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		1/5 (20%)		2/30 (6.7%)
Dry eye	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Eyelid ptosis	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Cataract	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Conjunctival haemorrhage	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Eye disorder	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Eye irritation	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Eye swelling	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Vision blurred	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		4/30 (13.3%)
Visual impairment	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Gastrointestinal disorders
Abdominal distension	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		1/30 (3.3%)
Abdominal pain	0/3 (0%)		2/6 (33.3%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Constipation	2/3 (66.7%)		3/6 (50%)		1/7 (14.3%)		0/5 (0%)		9/30 (30%)
Diarrhoea	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		1/5 (20%)		12/30 (40%)
Dyspepsia	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Flatulence	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Gastritis	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Gastrooesophageal reflux disease	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Melaena	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Nausea	2/3 (66.7%)		3/6 (50%)		0/7 (0%)		0/5 (0%)		11/30 (36.7%)
Oesophagitis	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Oral pain	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Stomatitis	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		4/30 (13.3%)
Tongue coated	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Vomiting	1/3 (33.3%)		2/6 (33.3%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
Dry mouth	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Gingival inflammation	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Palatal oedema	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Tongue disorder	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Toothache	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
General disorders
Asthenia	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		1/30 (3.3%)
Chest discomfort	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Chest pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		6/30 (20%)
Chills	0/3 (0%)		2/6 (33.3%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
Fatigue	1/3 (33.3%)		1/6 (16.7%)		2/7 (28.6%)		2/5 (40%)		21/30 (70%)
Gait disturbance	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Oedema peripheral	0/3 (0%)		0/6 (0%)		0/7 (0%)		3/5 (60%)		8/30 (26.7%)
Pain	0/3 (0%)		3/6 (50%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
Pyrexia	1/3 (33.3%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		8/30 (26.7%)
Catheter site erythema	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Catheter site pruritus	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Influenza like illness	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Injection site pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Injection site reaction	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Irritability	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Oedema	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Spinal pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Infections and infestations
Cellulitis	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Eye infection	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Fungal infection	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Herpes zoster	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Hordeolum	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Klebsiella bacteraemia	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Nasopharyngitis	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		4/30 (13.3%)
Pneumonia	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Respiratory tract infection	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Upper respiratory tract infection	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		2/5 (40%)		3/30 (10%)
Urinary tract infection	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Atypical pneumonia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Bronchitis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		4/30 (13.3%)
Bronchopneumonia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Endocarditis bacterial	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Infection	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Influenza	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Meningitis pneumococcal	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Oral candidiasis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Oral herpes	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Rhinitis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Sinusitis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Staphylococcal infection	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Tooth infection	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Viral infection	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
Injury, poisoning and procedural complications
Contusion	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		2/30 (6.7%)
Fall	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Overdose	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Bone contusion	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Muscle strain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Periorbital haematoma	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Periorbital haemorrhage	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Post procedural haemorrhage	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Postoperative wound complication	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Tendon rupture	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Wound	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Investigations
Alanine aminotransferase decreased	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Blood albumin decreased	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Blood bicarbonate decreased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Blood bicarbonate increased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		2/5 (40%)		0/30 (0%)
Blood bilirubin decreased	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Blood chloride increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Blood creatinine decreased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Blood creatinine increased	0/3 (0%)		0/6 (0%)		3/7 (42.9%)		0/5 (0%)		6/30 (20%)
Blood glucose increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		2/5 (40%)		0/30 (0%)
Blood lactate dehydrogenase increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		2/5 (40%)		0/30 (0%)
Blood phosphorus decreased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Blood phosphorus increased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		2/5 (40%)		0/30 (0%)
Blood potassium decreased	0/3 (0%)		1/6 (16.7%)		1/7 (14.3%)		1/5 (20%)		0/30 (0%)
Blood sodium decreased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		1/30 (3.3%)
Blood sodium increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Blood uric acid increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		1/30 (3.3%)
Body height decreased	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
General physical condition abnormal	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Haemoglobin decreased	0/3 (0%)		0/6 (0%)		2/7 (28.6%)		1/5 (20%)		2/30 (6.7%)
Neutrophil count decreased	0/3 (0%)		0/6 (0%)		3/7 (42.9%)		2/5 (40%)		0/30 (0%)
Platelet count decreased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		1/30 (3.3%)
Weight increased	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
White blood cell count decreased	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		2/5 (40%)		2/30 (6.7%)
Blood creatine increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
C-reactive protein increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Cardiac murmur	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Clostridium test positive	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Granulocyte count decreased	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Prothrombin time prolonged	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Troponin increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Weight decreased	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
pH urine increased	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Metabolism and nutrition disorders
Decreased appetite	1/3 (33.3%)		1/6 (16.7%)		0/7 (0%)		1/5 (20%)		4/30 (13.3%)
Dehydration	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Hypercalcaemia	0/3 (0%)		1/6 (16.7%)		2/7 (28.6%)		0/5 (0%)		0/30 (0%)
Hyperglycaemia	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		2/5 (40%)		3/30 (10%)
Hyperphosphataemia	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		1/30 (3.3%)
Hypoalbuminaemia	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Hypocalcaemia	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		1/30 (3.3%)
Hypokalaemia	0/3 (0%)		2/6 (33.3%)		1/7 (14.3%)		0/5 (0%)		5/30 (16.7%)
Hypomagnesaemia	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Hyponatraemia	0/3 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/5 (0%)		2/30 (6.7%)
Metabolic acidosis	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Overweight	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Hyperuricaemia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Hypophosphataemia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/3 (0%)		1/6 (16.7%)		2/7 (28.6%)		0/5 (0%)		6/30 (20%)
Arthritis	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Back pain	1/3 (33.3%)		1/6 (16.7%)		1/7 (14.3%)		2/5 (40%)		9/30 (30%)
Joint stiffness	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Muscle spasms	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		5/30 (16.7%)
Muscular weakness	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Musculoskeletal chest pain	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		4/30 (13.3%)
Musculoskeletal pain	1/3 (33.3%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		3/30 (10%)
Musculoskeletal stiffness	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Pain in extremity	0/3 (0%)		2/6 (33.3%)		0/7 (0%)		0/5 (0%)		8/30 (26.7%)
Pain in jaw	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Spinal disorder	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Bone pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Fasciitis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Fistula	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Flank pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Joint swelling	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Muscle twitching	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Neck pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Synovial cyst	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Synovitis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Neoplasm skin	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Plasmacytoma	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Nervous system disorders
Coordination abnormal	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Dizziness	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		6/30 (20%)
Headache	1/3 (33.3%)		1/6 (16.7%)		0/7 (0%)		1/5 (20%)		8/30 (26.7%)
Hypoaesthesia	2/3 (66.7%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Hypogeusia	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Neuropathy peripheral	1/3 (33.3%)		1/6 (16.7%)		1/7 (14.3%)		1/5 (20%)		9/30 (30%)
Anosmia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Disturbance in attention	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Dizziness postural	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Monoplegia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Paraesthesia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Peripheral sensory neuropathy	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Sciatica	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Psychiatric disorders
Anxiety	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Depression	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Hallucination	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Insomnia	2/3 (66.7%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Mental status changes	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Mood altered	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Stress	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Affective disorder	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Confusional state	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Listless	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Renal and urinary disorders
Renal injury	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Nocturia	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Renal failure	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Reproductive system and breast disorders
Vaginal discharge	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/3 (33.3%)		2/6 (33.3%)		1/7 (14.3%)		1/5 (20%)		7/30 (23.3%)
Dysphonia	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		1/30 (3.3%)
Dyspnoea	0/3 (0%)		1/6 (16.7%)		1/7 (14.3%)		2/5 (40%)		8/30 (26.7%)
Epistaxis	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Haemoptysis	0/3 (0%)		0/6 (0%)		1/7 (14.3%)		0/5 (0%)		1/30 (3.3%)
Hypoxia	0/3 (0%)		1/6 (16.7%)		1/7 (14.3%)		0/5 (0%)		0/30 (0%)
Nasal congestion	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Nasal dryness	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Pleural effusion	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Rhinitis allergic	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Rhinorrhoea	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		2/30 (6.7%)
Sneezing	1/3 (33.3%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Chronic obstructive pulmonary disease	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Dry throat	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Dyspnoea exertional	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
Hiccups	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Oropharyngeal pain	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		3/30 (10%)
Pleurisy	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Productive cough	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		4/30 (13.3%)
Rales	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Sinus congestion	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Skin and subcutaneous tissue disorders
Drug eruption	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Rash	0/3 (0%)		0/6 (0%)		2/7 (28.6%)		0/5 (0%)		2/30 (6.7%)
Rash erythematous	0/3 (0%)		0/6 (0%)		0/7 (0%)		1/5 (20%)		0/30 (0%)
Dry skin	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Ecchymosis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		2/30 (6.7%)
Erythema	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Hyperhidrosis	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Night sweats	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Social circumstances
Walking aid user	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Vascular disorders
Hot flush	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Hypertension	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		1/5 (20%)		4/30 (13.3%)
Orthostatic hypotension	0/3 (0%)		1/6 (16.7%)		0/7 (0%)		0/5 (0%)		0/30 (0%)
Circulatory collapse	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Haematoma	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)
Pallor	0/3 (0%)		0/6 (0%)		0/7 (0%)		0/5 (0%)		1/30 (3.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.