Study of Panobinostat in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed/Refractory Multiple Myeloma
- Conditions
- Relapse/Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT02290431
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description LBH589 + bortezomib + dexamethasone LBH589 (panobinostat) Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. LBH589 + bortezomib + dexamethasone dexamethasone Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off. LBH589 + bortezomib + dexamethasone bortezomib Participants were administered LBH589 (panobinostat)in combination with bortezomib and dexamethasone 2 weeks on/1 week off.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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
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
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)
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
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.
Minimal Response Rate (MRR) Per Investigator after 24 weeks (8 cycles; cycle = 21 days) MRR is based on modified EBMT criteria per investigator assessment
Trial Locations
- Locations (1)
Novartis Investigative Site
🇯🇵Tokushima, Japan