Panobinostat with bortezomib and dexamethasone in relapsed or relapsed-and-refractory multiple myeloma

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2015-001564-19-HU
• Date of registration: 20/05/2016
• Prospective Registration: Yes
• Primary sponsor: Secura Bio, Inc.
• Public title: Panobinostat with bortezomib and dexamethasone in relapsed or relapsed-and-refractory multiple myeloma
• Scientific title: A multicenter, randomized, open-label Phase 2 study evaluating the safety and efficacy of three different regimens of oral panobinostat in combination with subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed/refractory multiple myeloma who have been previously exposed to immunomodulatory agents
• Date of first enrolment: 07/07/2016
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001564-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, Hungary, Italy, Korea, Republic of, Lebanon, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Sweden, Thailand, Turkey, United States

Contacts

• Name: Clinical Help Desk
• Affiliation: Secura Bio, Inc.

• Name: Clinical Help Desk
• Affiliation: Secura Bio, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
- Multiple Myeloma as per IMWG 2014 definition
- Requiring treatment for relapsed or relapsed/refractory disease
- Measurable disease based on central protein assessment
- 1 to 4 prior lines of therapy
- Prior IMiD exposure
- Acceptable lab values prior to starting study treatment

Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 111
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 137

Exclusion criteria:
- Primary refractory myeloma
- Refractory to bortezomib i.e. patients who progressed while receiving salvage
therapy with BTZ, or patients who progressed within 60 days of their most recent BTZ containing treatment.
- Concomitant anti-cancer therapy (other than BTZ/Dex and bisphosphonates)
- Prior treatment with DAC inhibitors
- Clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 month prior to screening)
- Unresolved diarrhea = CTCAE grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)

Other protocol-defined exclusion criteria may apply.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Multiple Myeloma
MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Intervention(s)

Trade Name: Farydak
Product Name: Farydak
Product Code: LBH589
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Panobinostat
CAS Number: 404950-80-7
Current Sponsor code: LBH589
Other descriptive name: PANOBINOSTAT LACTATE ANHYDROUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Farydak
Product Name: Farydak
Product Code: LBH589
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Panobinostat
CAS Number: 404950-80-7
Current Sponsor code: LBH589
Other descriptive name: PANOBINOSTAT LACTATE ANHYDROUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Trade Name: Farydak
Product Name: Farydak
Product Code: LBH589
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Panobinostat
CAS Number: 404950-80-7
Current Sponsor code: LBH589
Other descriptive name: PANOBINOSTAT LACTATE ANHYDROUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Bortezomib
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1-

Trade Name: Dexamethasone
Product Name: Dexamethasone
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2

Product Name: Bortezomib
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: equal
Concentration number: 1-

Product Name: Bortezomib
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg/m2 milligram(s)/square meter
Concen

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: approximately after 30 months

Secondary Objective: - To assess overall response rate (ORR)
- To assess the individual iCR, sCR, CR, VGPR rates
- To assess progression free survival (PFS)
- To assess overall survival (OS)
- To evaluate overall safety of the combination of PAN, BTZ and Dex
- To assess pharmacokinetics
- To assess exposure-response (efficacy and safety) relationship
- To assess Time to Progression (TTP), Time to Response (TTR), Duration of Response (DOR)
- To assess health-related quality of life (HRQoL)

Primary end point(s): - ORR (according to IMWG criteria by IRC assessment) comprised of
immunophenotypic CR (iCR), stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)

Main Objective: - To assess overall response rate (ORR) up to 8 cycles

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - best ORR: approximately after 70 months
- individual iCR, sCR, CR, VGPR rates: approximatively after 30 and 70 months
- PFS: approximatively after 30 and 70 months
- OS: approximatively after 30 and 70 months
- Overall safety of combination of PAN, BTZ and Dex: approximatively after 30 and 70 months
- Pharmacokinetics: approximatively after 30 months
- Exposure-response:a pproximatively after 30 months
- TTP, TTR, DOR: approximatively after 30 and 70 months
- HRQoL: approximatively after 30 and 70 months

Secondary end point(s): - ORR (according to IMWG criteria by IRC assessment)
- iCR, sCR, CR, VGPR rates (according to IMWG criteria by IRC assessment)
- PFS (according to IMWG criteria by IRC assessment)
- OS
- AEs (graded by CTCAE v4.03), SAEs Abnormalities in vital signs, ECG
parameters, and laboratory test values. This will include events up to 30 days after discontinuation of study treatment.
- Cmax (PAN, BTZ), C24h (PAN), Cmin (BTZ) and AUC0-8h (PAN, BTZ)
- ORR, Grade 3/4 Thrombocytopenia, Grade 3/4 Diarrhea (relationship with PAN, BTZ PK parameters derived from NCA or Pop PK analysis)
- TTP, TTR, DOR (according to IMWG criteria by IRC assessment)
- HRQoL as measured by EORTC QLQ-C30 and FACT/GOG-Ntx

Secondary ID(s)

NCT02654990

CLBH589D2222

2015-001564-19-ES

Source(s) of Monetary Support

Secura Bio, Inc.

Ethics review

Status: Approved
Approval date: 22/06/2016
Contact: