Relapse/Refractory Multiple MyelomaPhase 2NCT02290431
Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma
A Phase 2 study testing LBH589 (panobinostat), bortezomib and dexamethasone in people with Relapse/Refractory Multiple Myeloma, run by Novartis Pharmaceuticals at 20 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapse/Refractory Multiple Myeloma
- What is being tested?
- LBH589 (panobinostat), bortezomib and dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 20 sitesJapan
- Study dates
- 16 Dec 2014to 25 Dec 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
Japan20 sites
Novartis Investigative Site
Aomori, 030 8553
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Higashiibaraki-gun, Ibaraki, 311-3193
Novartis Investigative Site
Kashiwa, Chiba, 277-8567
Novartis Investigative Site
Kobe, Hyōgo, 650-0047
Novartis Investigative Site
Koto Ku, Tokyo, 135 8550
Novartis Investigative Site
Kyoto, Kyoto, 602-8566
Novartis Investigative Site
Maebashi, Gunma, 371 8511
Novartis Investigative Site
Matsuyama, Ehime, 790-8524
Novartis Investigative Site
Nagoya, Aichi-ken, 467-8602
Novartis Investigative Site
Niigata, 951-8566
Novartis Investigative Site
Ōgaki, Gifu, 503-8502
Novartis Investigative Site
Okayama, Okayama-ken, 701-1192
Novartis Investigative Site
Sendai, Miyagi, 983 8520
Novartis Investigative Site
Shibukawa, Gunma, 377-0280
Novartis Investigative Site
Shibuya City, Tokyo, 150-8935
Novartis Investigative Site
Shinjuku Ku, Tokyo, 162 8655
Novartis Investigative Site
Suita, Osaka, 565 0871
Novartis Investigative Site
Tachikawa, Tokyo, 190-0014
Novartis Investigative Site
Tokushima, 770-8503
About this study
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
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.
- Conditions
- Relapse/Refractory Multiple Myeloma
- Being tested
- LBH589 (panobinostat), bortezomib, dexamethasone
- Keywords
- LBH589, panobinostat, bortezomib, dexamethasone, Phase II, bortezomib and dexamethasone, Japanese patients, relapsed/refractory multiple myeloma, Panobinostat (PAN)
- Medical subject headings
- Recurrence, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LBH589 (panobinostat)Drug
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)
bortezomibDrug
Bortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) \& treatment phase 2 (42 days).
dexamethasoneDrug
Dexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days \& treatment phase 2 (42 days)
| Study group | Role | What they receive |
|---|---|---|
| LBH589 + bortezomib + dexamethasone | Experimental | Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. Receives: Drug: LBH589 (panobinostat); Drug: bortezomib; Drug: dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: after 24 weeks (8 cycles; cycle = 21 days)
Secondary outcomes (15)
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
Measured: duration of study up to approx. 4 years
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
Measured: 24 weeks (8 cycles; cycle = 21 days)
Overall Survival (OS)
OS is defined as time from first dose of study treatment to death
Measured: up to 30 days after end of study, approx. 4 years
Minimal Response Rate (MRR) Per Investigator
MRR is based on modified EBMT criteria per investigator assessment
Measured: after 24 weeks (8 cycles; cycle = 21 days)
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
Measured: duration of study up to approx. 4 years
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
Measured: duration of study up to approx. 4 years
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
Measured: duration of study up to approx. 4 years
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.
Measured: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 156
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.
Measured: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
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.
Measured: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
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.
Measured: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
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
Measured: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z
Lambda_z: The terminal elimination rate constant (h-1)
Measured: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F
CL/F: The apparent total body clearance of drug from the plasma
Measured: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F
Vz/F: The apparent volume of distribution during terminal phase (associated with Lambda_z)
Measured: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2014 (estimated)
- Study start16 Dec 2014
- Primary completion29 Dec 2017
- Study completion25 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapse/Refractory Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02290431
- Sponsor's protocol ID
- CLBH589D1201
- Status last verified
- Oct 2019
- First submitted
- 24 Oct 2014
- Last updated
- 18 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
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.
PubMed 33279887
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02290431
- Acronym / sponsor ID
- CLBH589D1201
- Conditions
- Relapse/Refractory Multiple Myeloma
- Keywords
- LBH589, panobinostat, bortezomib, dexamethasone, Phase II, bortezomib and dexamethasone, Japanese patients, relapsed/refractory multiple myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Dec 2014 (actual)
- Primary completion
- 29 Dec 2017 (actual)
- Study completion
- 25 Dec 2018 (actual)
- First posted
- 14 Nov 2014 (estimated)
- Results
- Posted 18 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LBH589 + bortezomib + dexamethasone | Experimental | Drug: LBH589 (panobinostat), Drug: bortezomib, Drug: dexamethasoneParticipants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | LBH589 + bortezomib + dexamethasone |
| bortezomibBortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) \& treatment phase 2 (42 days). | Drug | LBH589 + bortezomib + dexamethasone |
| dexamethasoneDexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days \& treatment phase 2 (42 days) | Drug | LBH589 + bortezomib + dexamethasone |
Primary outcome
Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate
Time frame: 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.
15 secondary outcomes
Progression Free Survival (PFS)
Time frame: duration of study up to approx. 4 years
Overall Response Rate (ORR)
Time frame: 24 weeks (8 cycles; cycle = 21 days)
Overall Survival (OS)
Time frame: up to 30 days after end of study, approx. 4 years
Minimal Response Rate (MRR) Per Investigator
Time frame: after 24 weeks (8 cycles; cycle = 21 days)
Time to Response (TTR) Per Investigator
Time frame: duration of study up to approx. 4 years
Time to Progression/Relapse (TTP) Per Investigator
Time frame: duration of study up to approx. 4 years
Duration of Response (DOR) Per Investigator
Time frame: duration of study up to approx. 4 years
Quality of Life (QoL) as Measured by FACT/GOG-Ntx Total Score
Time frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 156
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: AUClast, AUC0-24h, AUC0-48h, AUCinf
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: T1/2
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F
Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33279887Suzuki 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.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LBH589 (panobinostat), bortezomib and dexamethasone in people with Relapse/Refractory Multiple Myeloma, run by Novartis Pharmaceuticals at 20 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Near Complete Response (nCR)/ Complete Response (CR) Rate (time frame: after 24 weeks (8 cycles; cycle = 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02290431, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2019.