Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02290431
Collaborator
(none)
31
20
1
48.3
1.6
0
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
31 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II, Multi-center, Single Arm, Open Label Study to Evaluate the Efficacy and Safety of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date
:
Dec 16, 2014
Actual Primary Completion Date
:
Dec 29, 2017
Actual Study Completion Date
:
Dec 25, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LBH589 + bortezomib + dexamethasone Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
Drug: LBH589 (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)
Drug: bortezomib
Bortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) & treatment phase 2 (42 days).
Drug: dexamethasone
Dexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days & treatment phase 2 (42 days)
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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)
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Nagoya-city | Aichi | Japan | 467-8602 |
| 2 | Novartis Investigative Site | Kashiwa-city | Chiba | Japan | 277-8567 |
| 3 | Novartis Investigative Site | Matsuyama-city | Ehime | Japan | 790-8524 |
| 4 | Novartis Investigative Site | Fukuoka city | Fukuoka | Japan | 812-8582 |
| 5 | Novartis Investigative Site | Ogaki-city | Gifu | Japan | 503-8502 |
| 6 | Novartis Investigative Site | Maebashi city | Gunma | Japan | 371 8511 |
| 7 | Novartis Investigative Site | Shibukawa-city | Gunma | Japan | 377-0280 |
| 8 | Novartis Investigative Site | Kobe-city | Hyogo | Japan | 650-0047 |
| 9 | Novartis Investigative Site | Higashiibaraki-gun | Ibaraki | Japan | 311-3193 |
| 10 | Novartis Investigative Site | Kyoto-city | Kyoto | Japan | 602-8566 |
| 11 | Novartis Investigative Site | Sendai-shi | Miyagi | Japan | 983 8520 |
| 12 | Novartis Investigative Site | Okayama city | Okayama | Japan | 701-1192 |
| 13 | Novartis Investigative Site | Suita city | Osaka | Japan | 565 0871 |
| 14 | Novartis Investigative Site | Koto ku | Tokyo | Japan | 135 8550 |
| 15 | Novartis Investigative Site | Shibuya | Tokyo | Japan | 150-8935 |
| 16 | Novartis Investigative Site | Shinjuku ku | Tokyo | Japan | 162 8655 |
| 17 | Novartis Investigative Site | Tachikawa | Tokyo | Japan | 190-0014 |
| 18 | Novartis Investigative Site | Aomori | Japan | 030 8553 | |
| 19 | Novartis Investigative Site | Niigata | Japan | 951-8566 | |
| 20 | Novartis Investigative Site | Tokushima | Japan | 770-8503 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02290431
Other Study ID Numbers:
- CLBH589D1201
First Posted:
Nov 14, 2014
Last Update Posted:
Nov 18, 2019
Last Verified:
Oct 1, 2019
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Period Title: Overall Study | |
| STARTED | 31 |
| Subjects. Discont. Prematurely | 27 |
| Subjects Completed Study Per Protocol | 8 |
| Subjs. Ntered Post-treatment Eval. Phase | 31 |
| Subjects Entered Survival f/u Phase | 24 |
| Entered Treatment Phase 2 | 17 |
| COMPLETED | 4 |
| NOT COMPLETED | 27 |
Baseline Characteristics
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Overall Participants | 31 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
67.8
(6.09)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
18
58.1%
|
| Male |
13
41.9%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| Japanese |
31
100%
|
Outcome Measures
| Title | Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Number (90% Confidence Interval) [Percentage of participants] |
48.4
156.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LBH589 + Bortezomib + Dexamethasone |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | single-sample binomial test | |
| Comments | ||
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Median (95% Confidence Interval) [months] |
15.3
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Number (95% Confidence Interval) [Percentage of participants] |
80.6
260%
|
| Title | Overall Survival (OS) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Minimal Response Rate (MRR) Per Investigator |
|---|---|
| Description | MRR is based on modified EBMT criteria per investigator assessment |
| Time Frame | after 24 weeks (8 cycles; cycle = 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Number [Percentage of participants] |
9.7
31.3%
|
| Title | Time to Response (TTR) Per Investigator |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Median (95% Confidence Interval) [months] |
1.4
|
| Title | Time to Progression/Relapse (TTP) Per Investigator |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Median (95% Confidence Interval) [months] |
15.3
|
| Title | Duration of Response (DOR) Per Investigator |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Median (95% Confidence Interval) [months] |
22.7
|
| Title | Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS: The FAS comprised of all subjects who took at least one dose of any study treatment component. |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 31 |
| Baseline |
112.33
|
| Week 12 |
91.75
|
| Week 24 |
100.33
|
| Week 36 |
125.83
|
| Week 48 |
114.25
|
| Week 60 |
109.92
|
| Week 72 |
108.00
|
| Week 84 |
101.00
|
| Week 96 |
121.67
|
| Week 108 |
120.17
|
| Week 120 |
125.25
|
| Week 132 |
114.00
|
| Week 156 |
119.8
|
| Title | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 8 |
| PAN: AUClast C1D1 |
106
(14.7)
|
| PAN: AUClast C1D8 |
156
(31.7)
|
| BJB432: AUClast C1D1 |
37.8
(38.2)
|
| BJB432: AUClast C1D8 |
166
(87.7)
|
| PAN: AUC0-24h C1D1 |
87.1
(13.7)
|
| PAN: AUC0-24h C1D8 |
125
(30.1)
|
| BJB432: AUC0-24h C1D1 |
18.5
(33.9)
|
| BJB432: AUC0-24h C1D8 |
83.8
(76.1)
|
| PAN: AUC0-48h C1D1 |
106
(14.8)
|
| PAN: AUC0-48h C1D8 |
156
(31.7)
|
| BJB432: AUC0-48h C1D1 |
36.8
(40.6)
|
| BJB432: AUC0-48h C1D8 |
169
(98.8)
|
| PAN: AUCinf C1D1 |
116
(15.5)
|
| PAN: AUCinf C1D8 |
175
(32.7)
|
| Title | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 8 |
| PAN: Cycle 1 Day 1 (C1D1) |
11.5
(30.4)
|
| PAN: Cycle 1 Day 8 (C1D8) |
18.2
(41.5)
|
| BJB432: C1D1 |
1.06
(42.1)
|
| BJB432: C1D8 |
4.38
(84.2)
|
| Title | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 8 |
| PAN: C1D1 |
2.00
|
| PAN: C1D8 |
2.00
|
| BJB432: C1D1 |
24.0
|
| BJB432: C1D8 |
24.0
|
| Title | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: T1/2 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 8 |
| PAN: C1D1 |
13.7
(21.7)
|
| PAN: C1D8 |
16.5
(5.2)
|
| Title | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z |
|---|---|
| Description | Lambda_z: The terminal elimination rate constant (h-1) |
| Time Frame | Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 8 |
| PAN: C1D1 |
0.0506
(21.7)
|
| PAN: C1D8 |
0.0421
(5.2)
|
| Title | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 8 |
| PAN: C1D1 |
172
(15.5)
|
| PAN: C1D8 |
114
(32.7)
|
| Title | Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LBH589 + Bortezomib + Dexamethasone |
|---|---|
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
| Measure Participants | 8 |
| PAN: C1D1 |
3390
(20.2)
|
| PAN: C1D8 |
2720
(31.6)
|
Adverse Events
| Time Frame | Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 985 days on panobinostat + bortezomib + dexamethasone (PAN + BTZ + Dex). | |
|---|---|---|
| Adverse Event Reporting Description | Adverse Event: Any sign or symptom that occurs during the study treatment plus 30 days post treatment. | |
| Arm/Group Title | LBH589 + Bortezomib + Dexamethasone | |
| Arm/Group Description | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. | |
All Cause Mortality |
||
| LBH589 + Bortezomib + Dexamethasone | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/31 (0%) | |
Serious Adverse Events |
||
| LBH589 + Bortezomib + Dexamethasone | ||
| Affected / at Risk (%) | # Events | |
| Total | 14/31 (45.2%) | |
| Blood and lymphatic system disorders | ||
| Coagulopathy | 1/31 (3.2%) | |
| Thrombocytopenia | 2/31 (6.5%) | |
| Eye disorders | ||
| Cataract | 1/31 (3.2%) | |
| General disorders | ||
| Asthenia | 1/31 (3.2%) | |
| Fatigue | 2/31 (6.5%) | |
| Malaise | 1/31 (3.2%) | |
| Pyrexia | 1/31 (3.2%) | |
| Infections and infestations | ||
| Herpes zoster | 1/31 (3.2%) | |
| Pneumonia | 4/31 (12.9%) | |
| Pyelonephritis | 1/31 (3.2%) | |
| Sepsis | 1/31 (3.2%) | |
| Investigations | ||
| Platelet count decreased | 2/31 (6.5%) | |
| Metabolism and nutrition disorders | ||
| Dehydration | 1/31 (3.2%) | |
| Nervous system disorders | ||
| Dizziness | 1/31 (3.2%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Interstitial lung disease | 1/31 (3.2%) | |
| Pneumonitis | 1/31 (3.2%) | |
| Vascular disorders | ||
| Hypertension | 1/31 (3.2%) | |
| Orthostatic hypotension | 1/31 (3.2%) | |
Other (Not Including Serious) Adverse Events |
||
| LBH589 + Bortezomib + Dexamethasone | ||
| Affected / at Risk (%) | # Events | |
| Total | 31/31 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 10/31 (32.3%) | |
| Leukopenia | 4/31 (12.9%) | |
| Lymphopenia | 5/31 (16.1%) | |
| Neutropenia | 7/31 (22.6%) | |
| Thrombocytopenia | 17/31 (54.8%) | |
| Eye disorders | ||
| Cataract | 3/31 (9.7%) | |
| Gastrointestinal disorders | ||
| Constipation | 13/31 (41.9%) | |
| Diarrhoea | 25/31 (80.6%) | |
| Dyspepsia | 2/31 (6.5%) | |
| Gastritis | 3/31 (9.7%) | |
| Nausea | 15/31 (48.4%) | |
| Stomatitis | 2/31 (6.5%) | |
| Vomiting | 9/31 (29%) | |
| General disorders | ||
| Face oedema | 2/31 (6.5%) | |
| Fatigue | 10/31 (32.3%) | |
| Injection site reaction | 3/31 (9.7%) | |
| Malaise | 10/31 (32.3%) | |
| Oedema peripheral | 8/31 (25.8%) | |
| Pyrexia | 7/31 (22.6%) | |
| Hepatobiliary disorders | ||
| Hepatic function abnormal | 4/31 (12.9%) | |
| Infections and infestations | ||
| Conjunctivitis | 2/31 (6.5%) | |
| Gastroenteritis | 2/31 (6.5%) | |
| Herpes zoster | 4/31 (12.9%) | |
| Nasopharyngitis | 7/31 (22.6%) | |
| Pharyngitis | 2/31 (6.5%) | |
| Upper respiratory tract infection | 5/31 (16.1%) | |
| Injury, poisoning and procedural complications | ||
| Contusion | 3/31 (9.7%) | |
| Investigations | ||
| Alanine aminotransferase increased | 2/31 (6.5%) | |
| Blood alkaline phosphatase increased | 2/31 (6.5%) | |
| Blood creatinine increased | 3/31 (9.7%) | |
| C-reactive protein increased | 3/31 (9.7%) | |
| Gamma-glutamyltransferase increased | 3/31 (9.7%) | |
| Lymphocyte count decreased | 7/31 (22.6%) | |
| Neutrophil count decreased | 9/31 (29%) | |
| Platelet count decreased | 9/31 (29%) | |
| Weight decreased | 4/31 (12.9%) | |
| White blood cell count decreased | 4/31 (12.9%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 18/31 (58.1%) | |
| Dehydration | 2/31 (6.5%) | |
| Hypermagnesaemia | 2/31 (6.5%) | |
| Hypoalbuminaemia | 2/31 (6.5%) | |
| Hypokalaemia | 6/31 (19.4%) | |
| Hyponatraemia | 2/31 (6.5%) | |
| Hypophosphataemia | 5/31 (16.1%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 4/31 (12.9%) | |
| Back pain | 3/31 (9.7%) | |
| Nervous system disorders | ||
| Dysgeusia | 7/31 (22.6%) | |
| Neuropathy peripheral | 6/31 (19.4%) | |
| Peripheral sensory neuropathy | 5/31 (16.1%) | |
| Somnolence | 2/31 (6.5%) | |
| Psychiatric disorders | ||
| Insomnia | 7/31 (22.6%) | |
| Renal and urinary disorders | ||
| Pollakiuria | 2/31 (6.5%) | |
| Renal impairment | 2/31 (6.5%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Hiccups | 2/31 (6.5%) | |
| Oropharyngeal pain | 2/31 (6.5%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash | 5/31 (16.1%) | |
| Vascular disorders | ||
| Hypertension | 4/31 (12.9%) | |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02290431
Other Study ID Numbers:
- CLBH589D1201
First Posted:
Nov 14, 2014
Last Update Posted:
Nov 18, 2019
Last Verified:
Oct 1, 2019