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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02290431
Recruitment Status : Completed
First Posted : November 14, 2014
Results First Posted : November 18, 2019
Last Update Posted : November 18, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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
Relapse/Refractory Multiple Myeloma Drug: LBH589 (panobinostat) Drug: bortezomib Drug: dexamethasone Phase 2

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Study Type : Interventional  (Clinical Trial)
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 : December 16, 2014
Actual Primary Completion Date : December 29, 2017
Actual Study Completion Date : December 25, 2018


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)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: 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

  2. Overall Response Rate (ORR) [ Time Frame: 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

  3. Overall Survival (OS) [ Time Frame: up to 30 days after end of study, approx. 4 years ]
    OS is defined as time from first dose of study treatment to death

  4. Minimal Response Rate (MRR) Per Investigator [ Time Frame: after 24 weeks (8 cycles; cycle = 21 days) ]
    MRR is based on modified EBMT criteria per investigator assessment

  5. Time to Response (TTR) Per Investigator [ Time Frame: 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

  6. Time to Progression/Relapse (TTP) Per Investigator [ Time Frame: 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

  7. Duration of Response (DOR) Per Investigator [ Time Frame: 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

  8. 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 ]
    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.

  9. 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 ]
    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.

  10. Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Cmax [ Time Frame: 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.

  11. Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Tmax [ Time Frame: 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.

  12. Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: T1/2 [ Time Frame: 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

  13. Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z [ Time Frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose ]
    Lambda_z: The terminal elimination rate constant (h-1)

  14. Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F [ Time Frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose ]
    CL/F: The apparent total body clearance of drug from the plasma

  15. Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F [ Time Frame: 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02290431


Locations
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Japan
Novartis Investigative Site
Nagoya-city, Aichi, Japan, 467-8602
Novartis Investigative Site
Kashiwa-city, Chiba, Japan, 277-8567
Novartis Investigative Site
Matsuyama-city, Ehime, Japan, 790-8524
Novartis Investigative Site
Fukuoka city, Fukuoka, Japan, 812-8582
Novartis Investigative Site
Ogaki-city, Gifu, Japan, 503-8502
Novartis Investigative Site
Maebashi city, Gunma, Japan, 371 8511
Novartis Investigative Site
Shibukawa-city, Gunma, Japan, 377-0280
Novartis Investigative Site
Kobe-city, Hyogo, Japan, 650-0047
Novartis Investigative Site
Higashiibaraki-gun, Ibaraki, Japan, 311-3193
Novartis Investigative Site
Kyoto-city, Kyoto, Japan, 602-8566
Novartis Investigative Site
Sendai-shi, Miyagi, Japan, 983 8520
Novartis Investigative Site
Okayama city, Okayama, Japan, 701-1192
Novartis Investigative Site
Suita city, Osaka, Japan, 565 0871
Novartis Investigative Site
Koto ku, Tokyo, Japan, 135 8550
Novartis Investigative Site
Shibuya, Tokyo, Japan, 150-8935
Novartis Investigative Site
Shinjuku ku, Tokyo, Japan, 162 8655
Novartis Investigative Site
Tachikawa, Tokyo, Japan, 190-0014
Novartis Investigative Site
Aomori, Japan, 030 8553
Novartis Investigative Site
Niigata, Japan, 951-8566
Novartis Investigative Site
Tokushima, Japan, 770-8503
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] November 19, 2018
Study Protocol  [PDF] February 27, 2018

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02290431    
Other Study ID Numbers: CLBH589D1201
First Posted: November 14, 2014    Key Record Dates
Results First Posted: November 18, 2019
Last Update Posted: November 18, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

URL: https://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
LBH589
panobinostat
bortezomib
dexamethasone
Phase II
bortezomib and dexamethasone
Japanese patients
relapsed/refractory multiple myeloma
Panobinostat (PAN)
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Bortezomib
Panobinostat
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors