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

Relapse/Refractory Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02290431
• Other study ID #: CLBH589D1201
• Status: Completed
• Phase: Phase 2
• Start date: December 16, 2014
• Est. completion date: December 25, 2018

Study information

• Verified date: October 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 25, 2018
• Est. primary completion date: December 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapse/Refractory Multiple Myeloma

Intervention

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)
• bortezomib
Bortezomib (BTZ) s.c: 1.3 mg/m2 was administered during both treatment phase 1 (21 days) & treatment phase 2 (42 days).
• dexamethasone
Dexamethasone (Dex): 20mg tablets taken during both treatment phase 1 (21 days & treatment phase 2 (42 days)

Locations

Country	Name	City	State
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Higashiibaraki-gun	Ibaraki
Japan	Novartis Investigative Site	Kashiwa-city	Chiba
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Koto ku	Tokyo
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Maebashi city	Gunma
Japan	Novartis Investigative Site	Matsuyama-city	Ehime
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Ogaki-city	Gifu
Japan	Novartis Investigative Site	Okayama city	Okayama
Japan	Novartis Investigative Site	Sendai-shi	Miyagi
Japan	Novartis Investigative Site	Shibukawa-city	Gunma
Japan	Novartis Investigative Site	Shibuya	Tokyo
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Japan	Novartis Investigative Site	Suita city	Osaka
Japan	Novartis Investigative Site	Tachikawa	Tokyo
Japan	Novartis Investigative Site	Tokushima

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	after 24 weeks (8 cycles; cycle = 21 days)
Secondary	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	duration of study up to approx. 4 years
Secondary	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	24 weeks (8 cycles; cycle = 21 days)
Secondary	Overall Survival (OS)	OS is defined as time from first dose of study treatment to death	up to 30 days after end of study, approx. 4 years
Secondary	Minimal Response Rate (MRR) Per Investigator	MRR is based on modified EBMT criteria per investigator assessment	after 24 weeks (8 cycles; cycle = 21 days)
Secondary	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	duration of study up to approx. 4 years
Secondary	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	duration of study up to approx. 4 years
Secondary	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	duration of study up to approx. 4 years
Secondary	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.	Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, and 156
Secondary	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.	Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Secondary	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.	Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Secondary	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.	Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h, 48h post dose
Secondary	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	Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Secondary	Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Lambda_z	Lambda_z: The terminal elimination rate constant (h-1)	Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Secondary	Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: CL/F	CL/F: The apparent total body clearance of drug from the plasma	Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose
Secondary	Composite PharmacoKinetics (PK) of Panobinostat and Bortezomib: Vz/F	Vz/F: The apparent volume of distribution during terminal phase (associated with Lambda_z)	Predose, 0.5h, 1h, 2h, 3h, 4h 8h, 24h 48h post dose