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

Novartis Pharmaceuticals31 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Relapse/Refractory Multiple Myeloma

Interventions

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)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (20)

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Kashiwa, Chiba, Japan

Outcomes

Primary Outcomes

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.

Time frame: after 24 weeks (8 cycles; cycle = 21 days)

Secondary Outcomes

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

Time frame: 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

Time frame: 24 weeks (8 cycles; cycle = 21 days)

Overall Survival (OS)

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

Minimal Response Rate (MRR) Per Investigator

MRR is based on modified EBMT criteria per investigator assessment

Time frame: 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

Time frame: duration of study up to approx. 4 years

Data from ClinicalTrials.gov

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Novartis Investigative Site

Matsuyama, Ehime, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Ōgaki, Gifu, Japan

Novartis Investigative Site

Maebashi, Gunma, Japan

Novartis Investigative Site

Shibukawa, Gunma, Japan

Novartis Investigative Site

Kobe, Hyōgo, Japan

Novartis Investigative Site

Higashiibaraki-gun, Ibaraki, Japan

Novartis Investigative Site

Kyoto, Kyoto, Japan

...and 10 more locations

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

Time frame: 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

Time frame: 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.

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

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

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.

Time frame: 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.

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose