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Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma

Primary Purpose

Relapse/Refractory Multiple Myeloma

Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
LBH589 (panobinostat)
bortezomib
dexamethasone
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapse/Refractory Multiple Myeloma focused on measuring LBH589, panobinostat, bortezomib, dexamethasone, Phase II, bortezomib and dexamethasone, Japanese patients, relapsed/refractory multiple myeloma, Panobinostat (PAN)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LBH589 + bortezomib + dexamethasone

Arm Description

Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
Overall Survival (OS)
OS is defined as time from first dose of study treatment to death
Minimal Response Rate (MRR) Per Investigator
MRR is based on modified EBMT criteria per investigator assessment
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 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
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
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.
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.
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.
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.
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
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z
Lambda_z: The terminal elimination rate constant (h-1)
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F
CL/F: The apparent total body clearance of drug from the plasma
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F
Vz/F: The apparent volume of distribution during terminal phase (associated with Lambda_z)

Full Information

First Posted
October 24, 2014
Last Updated
October 28, 2019
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02290431
Brief Title
Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
December 16, 2014 (Actual)
Primary Completion Date
December 29, 2017 (Actual)
Study Completion Date
December 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapse/Refractory Multiple Myeloma
Keywords
LBH589, panobinostat, bortezomib, dexamethasone, Phase II, bortezomib and dexamethasone, Japanese patients, relapsed/refractory multiple myeloma, Panobinostat (PAN)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LBH589 + bortezomib + dexamethasone
Arm Type
Experimental
Arm Description
Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off.
Intervention Type
Drug
Intervention Name(s)
LBH589 (panobinostat)
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
bortezomib
Intervention Description
Bortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) & treatment phase 2 (42 days).
Intervention Type
Drug
Intervention Name(s)
dexamethasone
Intervention Description
Dexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days & treatment phase 2 (42 days)
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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
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)
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
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)
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
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
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
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
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
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
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Nagoya-city
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
Novartis Investigative Site
City
Kashiwa-city
State/Province
Chiba
ZIP/Postal Code
277-8567
Country
Japan
Facility Name
Novartis Investigative Site
City
Matsuyama-city
State/Province
Ehime
ZIP/Postal Code
790-8524
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Ogaki-city
State/Province
Gifu
ZIP/Postal Code
503-8502
Country
Japan
Facility Name
Novartis Investigative Site
City
Maebashi city
State/Province
Gunma
ZIP/Postal Code
371 8511
Country
Japan
Facility Name
Novartis Investigative Site
City
Shibukawa-city
State/Province
Gunma
ZIP/Postal Code
377-0280
Country
Japan
Facility Name
Novartis Investigative Site
City
Kobe-city
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Facility Name
Novartis Investigative Site
City
Higashiibaraki-gun
State/Province
Ibaraki
ZIP/Postal Code
311-3193
Country
Japan
Facility Name
Novartis Investigative Site
City
Kyoto-city
State/Province
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai-shi
State/Province
Miyagi
ZIP/Postal Code
983 8520
Country
Japan
Facility Name
Novartis Investigative Site
City
Okayama city
State/Province
Okayama
ZIP/Postal Code
701-1192
Country
Japan
Facility Name
Novartis Investigative Site
City
Suita city
State/Province
Osaka
ZIP/Postal Code
565 0871
Country
Japan
Facility Name
Novartis Investigative Site
City
Koto ku
State/Province
Tokyo
ZIP/Postal Code
135 8550
Country
Japan
Facility Name
Novartis Investigative Site
City
Shibuya
State/Province
Tokyo
ZIP/Postal Code
150-8935
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku ku
State/Province
Tokyo
ZIP/Postal Code
162 8655
Country
Japan
Facility Name
Novartis Investigative Site
City
Tachikawa
State/Province
Tokyo
ZIP/Postal Code
190-0014
Country
Japan
Facility Name
Novartis Investigative Site
City
Aomori
ZIP/Postal Code
030 8553
Country
Japan
Facility Name
Novartis Investigative Site
City
Niigata
ZIP/Postal Code
951-8566
Country
Japan
Facility Name
Novartis Investigative Site
City
Tokushima
ZIP/Postal Code
770-8503
Country
Japan

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
33279887
Citation
Suzuki K, Sunami K, Matsumoto M, Maki A, Shimada F, Suzuki K, Shimizu K. Phase II, Multicenter, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of Panobinostat in Combination with Bortezomib and Dexamethasone in Japanese Patients with Relapsed or Relapsed-and-Refractory Multiple Myeloma. Acta Haematol. 2021;144(3):264-274. doi: 10.1159/000508529. Epub 2020 Dec 4.
Results Reference
derived

Learn more about this trial

Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma

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