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Completed

NCT Number: NCT02290431

Study 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.

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Key information

Conditions

Relapse/Refractory Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Multiple Myeloma Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Nagoya, Aichi-ken, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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)

bortezomib

Drug

Bortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) & treatment phase 2 (42 days).

Dexamethasone

Drug

Dexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days & treatment phase 2 (42 days)

Primary outcomes

  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 outcomes

  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)

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2014
Primary completion
2017
Study completion
2018
First posted
Nov 14, 2014
Registry last updated
Nov 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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