Relapse/Refractory Multiple Myeloma
Conditions
Keywords
LBH589, panobinostat, bortezomib, dexamethasone, Phase II, bortezomib and dexamethasone, Japanese patients, relapsed/refractory multiple myeloma, Panobinostat (PAN)
Brief summary
The purpose of this study was to evaluate the efficacy and safety of panobinostat in combination with bortezomib and dexamethasone in Japanese patients with relapsed/refractory multiple myeloma.
Interventions
DRUGLBH589 (panobinostat)
Panobinostat (PAN) capsules were supplied at dose strengths of 10 mg and 15 mg. and dosed at 20mg during treatment phase 1 (21 days) and treatment phase 2 (42 days)
DRUGbortezomib
Bortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) & treatment phase 2 (42 days).
DRUGdexamethasone
Dexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days & treatment phase 2 (42 days)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient had a previous diagnosis of multiple myeloma * Patient required retreatment for multiple myeloma * Patient had measurable M component in serum or urine at study screening
Exclusion criteria
* Primary refractory disease (patients that never reached at least an minor response for over 60 days under any prior therapy) * Patient who had been treated by bortezomib before, and did not reach at least a minor response under this therapy, or progressed under it or within 60 days of last dose * Patient received prior treatment with DAC inhibitors including panobinostat * Patient had impaired cardiac function, or a prolonged QTc interval at screening ECG
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate | after 24 weeks (8 cycles; cycle = 21 days) | nCR plus CR rate after 8 cycles of therapy as defined by the modified European Society for Bone and Marrow Transplantation (EBMT) criteria per investigator assessment as the proportion of participants with nCR or CR as their best overall response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | duration of study up to approx. 4 years | PFS is defined as time from first dose of study treatment to progression or death due to any cause, based on modified European Society for Bone and Marrow Transplantation (EBMT) criteria per Investigator's assessment |
| Overall Response Rate (ORR) | 24 weeks (8 cycles; cycle = 21 days) | ORR is defined as the proportion of participants with CR, nCR or partial response (PR) based on modified EBMT criteria per investigator assessment |
| Overall Survival (OS) | up to 30 days after end of study, approx. 4 years | OS is defined as time from first dose of study treatment to death |
| Minimal Response Rate (MRR) Per Investigator | after 24 weeks (8 cycles; cycle = 21 days) | MRR is based on modified EBMT criteria per investigator assessment |
| Time to Response (TTR) Per Investigator | duration of study up to approx. 4 years | TTR is defined as the time from the date of first dose of study treatment to first documented response (PR or nCR or CR) per modified EBMT criteria as assessed by investigator |
| Time to Progression/Relapse (TTP) Per Investigator | duration of study up to approx. 4 years | TTP is defined as the time from the date of the first dose of study treatment to the date of the first documented disease progression or relapse |
| Duration of Response (DOR) Per Investigator | duration of study up to approx. 4 years | DOR is defined as the time from date of the first documented CR/nCR or PR to the date of the first documented progression or relapse or death due to MM |
| Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 156 | QoL as measured by Functional Assessment of Cancer Therapy/ Gynecology Oncology Group Neurotoxicity (FACT/GOG-NTX) scale calculated scores and changes from baseline were summarized by visit. The FACT/GOG-Ntx is a measure to assess neurotoxicity from systemic chemotherapy. The recall period for this measure is the past 7 days. FACT/GOG-Ntx Total Score: 0 - 152 (28 + 28 + 24 + 28 + 44 = 152). (FACT-G Physical Well-Being Score: 0 - 28, FACT-G Social/Family Well-Being Score: 0 - 28, FACT-G Emotional Well-Being Score: 0 - 24, FACT-G Functional Well-Being Score: 0 - 28, FACT/GOG-Ntx Neurotoxicity Subscale Score: 0 - 44). 4. The scales are combined. The higher the score, the better the QOL. |
| Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose | PK sample collection was performed in subjects who agreed to blood samplings for the PK assessments of PAN and BTZ. The order of administration of the 3 study treatment components was 1) PAN, 2) Dex, and 3) BTZ. |
| Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose | Cmax: The maximum (peak) observed plasma concentration. PK sample collection was performed in subjects who agreed to blood samplings for the PK assessments of PAN and BTZ. The order of administration of the 3 study treatment components was 1) PAN, 2) Dex, and 3) BTZ. |
| Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose | Tmax: The time to reach maximum (peak) plasma concentration. PK sample collection was performed in subjects who agreed to blood samplings for the PK assessments of PAN and BTZ. The order of administration of the 3 study treatment components was 1) PAN, 2) Dex, and 3) BTZ. |
| Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: T1/2 | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose | T1/2: The elimination half-life associated with the terminal slope (Lambda\_z) of a semi logarithmic concentration-time curve |
| Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose | Lambda\_z: The terminal elimination rate constant (h-1) |
| Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose | CL/F: The apparent total body clearance of drug from the plasma |
| Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose | Vz/F: The apparent volume of distribution during terminal phase (associated with Lambda\_z) |
Countries
Japan
Participant flow
Recruitment details
Approximately 33 eligible subjects were planned to be enrolled. 31 eligible subjects were enrolled and treated with PAN+BTZ+Dex (Treatment phase 1), of which 17 subjects entered Treatment phase 2. All 31 subjects entered the post-treatment evaluation phase, of which 22 discontinued the study. 24 subjects entered the survival follow-up phase.
Participants by arm
| Arm | Count |
|---|---|
| LBH589 + Bortezomib + Dexamethasone Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Progressive disease | 4 |
| Overall Study | Study terminated by Sponsor | 1 |
Baseline characteristics
| Characteristic | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Age, Continuous | 67.8 years STANDARD_DEVIATION 6.09 |
| Race/Ethnicity, Customized Japanese | 31 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 14 / 31 |
Outcome results
Primary
Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate
nCR plus CR rate after 8 cycles of therapy as defined by the modified European Society for Bone and Marrow Transplantation (EBMT) criteria per investigator assessment as the proportion of participants with nCR or CR as their best overall response.
Time frame: after 24 weeks (8 cycles; cycle = 21 days)
Population: Full Analysis Set (FAS): The Full analysis set (FAS) comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate | 48.4 Percentage of participants |
p-value: <0.0001single-sample binomial test
Secondary
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf
PK sample collection was performed in subjects who agreed to blood samplings for the PK assessments of PAN and BTZ. The order of administration of the 3 study treatment components was 1) PAN, 2) Dex, and 3) BTZ.
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Population: PAS: Pharmacokinetic Analysis Set (PAS): The PK analysis set for PAN (PAS-PAN) consisted of all subjects with at least one evaluable PK concentration of PAN. The PK analysis set for BTZ (PAS-BTZ) consisted of all subjects with at least one evaluable PK concentration of BTZ.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | BJB432: AUClast C1D1 | 37.8 h.ng/mL | Geometric Coefficient of Variation 38.2 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUClast C1D1 | 106 h.ng/mL | Geometric Coefficient of Variation 14.7 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUClast C1D8 | 156 h.ng/mL | Geometric Coefficient of Variation 31.7 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | BJB432: AUClast C1D8 | 166 h.ng/mL | Geometric Coefficient of Variation 87.7 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUC0-24h C1D1 | 87.1 h.ng/mL | Geometric Coefficient of Variation 13.7 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUC0-24h C1D8 | 125 h.ng/mL | Geometric Coefficient of Variation 30.1 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | BJB432: AUC0-24h C1D1 | 18.5 h.ng/mL | Geometric Coefficient of Variation 33.9 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | BJB432: AUC0-24h C1D8 | 83.8 h.ng/mL | Geometric Coefficient of Variation 76.1 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUC0-48h C1D1 | 106 h.ng/mL | Geometric Coefficient of Variation 14.8 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUC0-48h C1D8 | 156 h.ng/mL | Geometric Coefficient of Variation 31.7 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | BJB432: AUC0-48h C1D1 | 36.8 h.ng/mL | Geometric Coefficient of Variation 40.6 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | BJB432: AUC0-48h C1D8 | 169 h.ng/mL | Geometric Coefficient of Variation 98.8 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUCinf C1D1 | 116 h.ng/mL | Geometric Coefficient of Variation 15.5 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf | PAN: AUCinf C1D8 | 175 h.ng/mL | Geometric Coefficient of Variation 32.7 |
Secondary
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F
CL/F: The apparent total body clearance of drug from the plasma
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Population: PAS: Pharmacokinetic Analysis Set (PAS): The PK analysis set for PAN (PAS-PAN) consisted of all subjects with at least one evaluable PK concentration of PAN. The PK analysis set for BTZ (PAS-BTZ) consisted of all subjects with at least one evaluable PK concentration of BTZ.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F | PAN: C1D1 | 172 Litre/hour (L/h) | Geometric Coefficient of Variation 15.5 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F | PAN: C1D8 | 114 Litre/hour (L/h) | Geometric Coefficient of Variation 32.7 |
Secondary
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax
Cmax: The maximum (peak) observed plasma concentration. PK sample collection was performed in subjects who agreed to blood samplings for the PK assessments of PAN and BTZ. The order of administration of the 3 study treatment components was 1) PAN, 2) Dex, and 3) BTZ.
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Population: Pharmacokinetic Analysis Set (PAS): The PK analysis set for PAN (PAS-PAN) consisted of all subjects with at least one evaluable PK concentration of PAN. The PK analysis set for BTZ (PAS-BTZ) consisted of all subjects with at least one evaluable PK concentration of BTZ.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax | PAN: Cycle 1 Day 1 (C1D1) | 11.5 ng/mL | Geometric Coefficient of Variation 30.4 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax | PAN: Cycle 1 Day 8 (C1D8) | 18.2 ng/mL | Geometric Coefficient of Variation 41.5 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax | BJB432: C1D1 | 1.06 ng/mL | Geometric Coefficient of Variation 42.1 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax | BJB432: C1D8 | 4.38 ng/mL | Geometric Coefficient of Variation 84.2 |
Secondary
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z
Lambda\_z: The terminal elimination rate constant (h-1)
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Population: PAS: Pharmacokinetic Analysis Set (PAS): The PK analysis set for PAN (PAS-PAN) consisted of all subjects with at least one evaluable PK concentration of PAN. The PK analysis set for BTZ (PAS-BTZ) consisted of all subjects with at least one evaluable PK concentration of BTZ.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z | PAN: C1D1 | 0.0506 1/hour (1/h) | Geometric Coefficient of Variation 21.7 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z | PAN: C1D8 | 0.0421 1/hour (1/h) | Geometric Coefficient of Variation 5.2 |
Secondary
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: T1/2
T1/2: The elimination half-life associated with the terminal slope (Lambda\_z) of a semi logarithmic concentration-time curve
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Population: PAS: Pharmacokinetic Analysis Set (PAS): The PK analysis set for PAN (PAS-PAN) consisted of all subjects with at least one evaluable PK concentration of PAN. The PK analysis set for BTZ (PAS-BTZ) consisted of all subjects with at least one evaluable PK concentration of BTZ.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: T1/2 | PAN: C1D1 | 13.7 hour (h) | Geometric Coefficient of Variation 21.7 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: T1/2 | PAN: C1D8 | 16.5 hour (h) | Geometric Coefficient of Variation 5.2 |
Secondary
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax
Tmax: The time to reach maximum (peak) plasma concentration. PK sample collection was performed in subjects who agreed to blood samplings for the PK assessments of PAN and BTZ. The order of administration of the 3 study treatment components was 1) PAN, 2) Dex, and 3) BTZ.
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Population: PAS: Pharmacokinetic Analysis Set (PAS): The PK analysis set for PAN (PAS-PAN) consisted of all subjects with at least one evaluable PK concentration of PAN. The PK analysis set for BTZ (PAS-BTZ) consisted of all subjects with at least one evaluable PK concentration of BTZ.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax | PAN: C1D1 | 2.00 hour (h) |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax | PAN: C1D8 | 2.00 hour (h) |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax | BJB432: C1D1 | 24.0 hour (h) |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax | BJB432: C1D8 | 24.0 hour (h) |
Secondary
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F
Vz/F: The apparent volume of distribution during terminal phase (associated with Lambda\_z)
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Population: PAS: Pharmacokinetic Analysis Set (PAS): The PK analysis set for PAN (PAS-PAN) consisted of all subjects with at least one evaluable PK concentration of PAN. The PK analysis set for BTZ (PAS-BTZ) consisted of all subjects with at least one evaluable PK concentration of BTZ.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F | PAN: C1D1 | 3390 Litre (L) | Geometric Coefficient of Variation 20.2 |
| LBH589 + Bortezomib + Dexamethasone | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F | PAN: C1D8 | 2720 Litre (L) | Geometric Coefficient of Variation 31.6 |
Secondary
Duration of Response (DOR) Per Investigator
DOR is defined as the time from date of the first documented CR/nCR or PR to the date of the first documented progression or relapse or death due to MM
Time frame: duration of study up to approx. 4 years
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Duration of Response (DOR) Per Investigator | 22.7 months |
Secondary
Minimal Response Rate (MRR) Per Investigator
MRR is based on modified EBMT criteria per investigator assessment
Time frame: after 24 weeks (8 cycles; cycle = 21 days)
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Minimal Response Rate (MRR) Per Investigator | 9.7 Percentage of participants |
Secondary
Overall Response Rate (ORR)
ORR is defined as the proportion of participants with CR, nCR or partial response (PR) based on modified EBMT criteria per investigator assessment
Time frame: 24 weeks (8 cycles; cycle = 21 days)
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Overall Response Rate (ORR) | 80.6 Percentage of participants |
Secondary
Overall Survival (OS)
OS is defined as time from first dose of study treatment to death
Time frame: up to 30 days after end of study, approx. 4 years
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Overall Survival (OS) | NA months |
Secondary
Progression Free Survival (PFS)
PFS is defined as time from first dose of study treatment to progression or death due to any cause, based on modified European Society for Bone and Marrow Transplantation (EBMT) criteria per Investigator's assessment
Time frame: duration of study up to approx. 4 years
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Progression Free Survival (PFS) | 15.3 months |
Secondary
Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score
QoL as measured by Functional Assessment of Cancer Therapy/ Gynecology Oncology Group Neurotoxicity (FACT/GOG-NTX) scale calculated scores and changes from baseline were summarized by visit. The FACT/GOG-Ntx is a measure to assess neurotoxicity from systemic chemotherapy. The recall period for this measure is the past 7 days. FACT/GOG-Ntx Total Score: 0 - 152 (28 + 28 + 24 + 28 + 44 = 152). (FACT-G Physical Well-Being Score: 0 - 28, FACT-G Social/Family Well-Being Score: 0 - 28, FACT-G Emotional Well-Being Score: 0 - 24, FACT-G Functional Well-Being Score: 0 - 28, FACT/GOG-Ntx Neurotoxicity Subscale Score: 0 - 44). 4. The scales are combined. The higher the score, the better the QOL.
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 156
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Baseline | 112.33 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 12 | 91.75 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 24 | 100.33 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 36 | 125.83 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 48 | 114.25 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 60 | 109.92 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 72 | 108.00 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 84 | 101.00 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 96 | 121.67 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 108 | 120.17 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 120 | 125.25 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 132 | 114.00 scores on a scale |
| LBH589 + Bortezomib + Dexamethasone | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score | Week 156 | 119.8 scores on a scale |
Secondary
Time to Progression/Relapse (TTP) Per Investigator
TTP is defined as the time from the date of the first dose of study treatment to the date of the first documented disease progression or relapse
Time frame: duration of study up to approx. 4 years
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Time to Progression/Relapse (TTP) Per Investigator | 15.3 months |
Secondary
Time to Response (TTR) Per Investigator
TTR is defined as the time from the date of first dose of study treatment to first documented response (PR or nCR or CR) per modified EBMT criteria as assessed by investigator
Time frame: duration of study up to approx. 4 years
Population: FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LBH589 + Bortezomib + Dexamethasone | Time to Response (TTR) Per Investigator | 1.4 months |