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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02654990




Registration number
NCT02654990
Ethics application status
Date submitted
16/12/2015
Date registered
13/01/2016
Date last updated
22/12/2023

Titles & IDs
Public title
Panobinostat/Bortezomib/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
Secondary ID [1] 0 0
2015-001564-19
Secondary ID [2] 0 0
CLBH589D2222
Universal Trial Number (UTN)
Trial acronym
PANORAMA_3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - panobinostat capsules
Treatment: Drugs - bortezomib injection
Treatment: Drugs - dexamethasone tablets

Experimental: Arm A - 20mg PAN TIW - 20mg panobinostat three times a week, 2 weeks on/1 week of in combination with s.c. bortezomib and p.o. dexamethasone

Experimental: Arm B - 20mg PAN BIW - 20mg panobinostat twice a week, 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone

Experimental: Arm C - 10mg PAN TIW - 10mg panobinostat three times a week 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone


Treatment: Drugs: panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)

Treatment: Drugs: bortezomib injection
1.3mg/m^2 sub-cutaneous administration; Cycle 1-4: 2 weeks on/1 week off twice a week for patients = 75 years at time of screening; once a week for patient > 75 years Cycle 5+: once a week for all patients

Treatment: Drugs: dexamethasone tablets
pre and 24h after BTZ administration; patients = 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall response rate (ORR) up to 8 cycles
Timepoint [1] 0 0
up to 8 cycles per patient, approximately 30 months
Secondary outcome [1] 0 0
ORR throughout study
Timepoint [1] 0 0
approximately 70 months
Secondary outcome [2] 0 0
individual immunophenotypic complete response (CR) rate
Timepoint [2] 0 0
approximately 30 and 70 months
Secondary outcome [3] 0 0
Progression-free survival
Timepoint [3] 0 0
approximately 30 and 70 months
Secondary outcome [4] 0 0
Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ)
Timepoint [4] 0 0
approximately 30 months
Secondary outcome [5] 0 0
Time to progression
Timepoint [5] 0 0
approximately 30 and 70 months
Secondary outcome [6] 0 0
Time to response
Timepoint [6] 0 0
approximately 30 and 70 months
Secondary outcome [7] 0 0
Duration of response (DOR)
Timepoint [7] 0 0
approximately 30 and 70 months
Secondary outcome [8] 0 0
European Organization of Research and Treatment of Cancer Quality of Life core 30-item questionnaire scores over time compared
Timepoint [8] 0 0
approximately 30 and 70 months
Secondary outcome [9] 0 0
individual stringent CR rate
Timepoint [9] 0 0
approximately 30 and 70 months
Secondary outcome [10] 0 0
individual CR rate
Timepoint [10] 0 0
approximately 30 and 70 months
Secondary outcome [11] 0 0
overall survival
Timepoint [11] 0 0
approximately 30 and 70 months
Secondary outcome [12] 0 0
individual Very Good Partial Response rate
Timepoint [12] 0 0
approximately 30 and 70 months
Secondary outcome [13] 0 0
Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time
Timepoint [13] 0 0
approximately 30 and 70 months
Secondary outcome [14] 0 0
Time to reach Cmax for PAN and BTZ
Timepoint [14] 0 0
approximately 30 months
Secondary outcome [15] 0 0
Minimum observed plasma concentration (Cmin) for PAN and BTZ
Timepoint [15] 0 0
approximately 30 months
Secondary outcome [16] 0 0
Observed plasma concentration 24 hours after single and multiple dose administration of PAN and BTZ
Timepoint [16] 0 0
24 hours after every dose, approximately 30 months

Eligibility
Key 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 randomization
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- primary refractory myeloma

- refractory to bortezomib

- 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 months prior to randomization)

- 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 inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/04/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/08/2022
Sample size
Target
Accrual to date
Final
249
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
West Virginia
Country [10] 0 0
Belgium
State/province [10] 0 0
Hasselt
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Czechia
State/province [15] 0 0
Czech Republic
Country [16] 0 0
Czechia
State/province [16] 0 0
Praha
Country [17] 0 0
France
State/province [17] 0 0
Bayonne Cedex
Country [18] 0 0
France
State/province [18] 0 0
Avignon Cedex 9
Country [19] 0 0
France
State/province [19] 0 0
Grenoble
Country [20] 0 0
France
State/province [20] 0 0
La Roche sur Yon Cedex
Country [21] 0 0
France
State/province [21] 0 0
Lille
Country [22] 0 0
France
State/province [22] 0 0
Metz
Country [23] 0 0
France
State/province [23] 0 0
Nantes Cedex 1
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
France
State/province [25] 0 0
Pessac
Country [26] 0 0
Germany
State/province [26] 0 0
Bad Saarow
Country [27] 0 0
Germany
State/province [27] 0 0
Bayreuth
Country [28] 0 0
Germany
State/province [28] 0 0
Darmstadt
Country [29] 0 0
Germany
State/province [29] 0 0
Dresden
Country [30] 0 0
Germany
State/province [30] 0 0
Halle Saale
Country [31] 0 0
Germany
State/province [31] 0 0
Hamburg
Country [32] 0 0
Germany
State/province [32] 0 0
Kiel
Country [33] 0 0
Germany
State/province [33] 0 0
Leipzig
Country [34] 0 0
Greece
State/province [34] 0 0
Athens
Country [35] 0 0
Greece
State/province [35] 0 0
Patras
Country [36] 0 0
Hungary
State/province [36] 0 0
HUN
Country [37] 0 0
Hungary
State/province [37] 0 0
Budapest
Country [38] 0 0
Hungary
State/province [38] 0 0
Kaposvar
Country [39] 0 0
Hungary
State/province [39] 0 0
Nyiregyhaza
Country [40] 0 0
Italy
State/province [40] 0 0
RM
Country [41] 0 0
Italy
State/province [41] 0 0
RN
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Hwasun
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Seoul
Country [44] 0 0
Lebanon
State/province [44] 0 0
Beirut
Country [45] 0 0
Lebanon
State/province [45] 0 0
Sidon
Country [46] 0 0
Netherlands
State/province [46] 0 0
Amsterdam
Country [47] 0 0
Netherlands
State/province [47] 0 0
Dordrecht
Country [48] 0 0
Norway
State/province [48] 0 0
Oslo
Country [49] 0 0
Poland
State/province [49] 0 0
Lublin
Country [50] 0 0
Poland
State/province [50] 0 0
Torun
Country [51] 0 0
Poland
State/province [51] 0 0
Warszawa
Country [52] 0 0
Poland
State/province [52] 0 0
Wroclaw
Country [53] 0 0
Portugal
State/province [53] 0 0
Braga
Country [54] 0 0
Portugal
State/province [54] 0 0
Porto
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Saint Petersburg
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Saratov
Country [57] 0 0
Spain
State/province [57] 0 0
Andalucia
Country [58] 0 0
Spain
State/province [58] 0 0
Castilla Y Leon
Country [59] 0 0
Spain
State/province [59] 0 0
Catalunya
Country [60] 0 0
Spain
State/province [60] 0 0
Santa Cruz De Tenerife
Country [61] 0 0
Spain
State/province [61] 0 0
Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Zaragoza
Country [63] 0 0
Sweden
State/province [63] 0 0
Lulea
Country [64] 0 0
Sweden
State/province [64] 0 0
Lund
Country [65] 0 0
Sweden
State/province [65] 0 0
Uppsala
Country [66] 0 0
Thailand
State/province [66] 0 0
Muang
Country [67] 0 0
Thailand
State/province [67] 0 0
Bangkok
Country [68] 0 0
Thailand
State/province [68] 0 0
Chiang Mai
Country [69] 0 0
Turkey
State/province [69] 0 0
Ankara
Country [70] 0 0
Turkey
State/province [70] 0 0
Istanbul
Country [71] 0 0
Turkey
State/province [71] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
pharmaand GmbH
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
NOTE: The study data was transferred to zr pharma& following the divestment of Panobinostat
to pharma&. Prior to study completion under the sponsorship of Secura Bio, the study was
initiated and conducted in part under the sponsorship of Novartis.

The purpose of this study is to investigate the safety and efficacy of three different
regimens of PAN (20 mg TIW, 20 mg BIW, and 10 mg TIW) in combination with s.c. BTZ and Dex
and to provide exposure, safety and efficacy data to identify the optimal regimen of PAN in a
randomized, 3-arm parallel design. This study will also assess the impact of administering
s.c. BTZ (in combination with PAN and Dex) twice weekly for 4 cycles, and then weekly
starting from Cycle 5 until disease progression in patients = 75 years of age. Patients > 75
years of age will receive for the entire treatment period s.c. BTZ weekly (in combination
with PAN and Dex) until disease progression.

Patients will be treated until disease progression or until they discontinue earlier due to
unacceptable toxicity or for other reasons.

Patients who discontinued study treatment for reasons other than disease progression will be
followed for efficacy every 6 weeks.

All patients will be followed for survival until the last patient entering long-term
follow-up has completed a 3-year survival follow-up or discontinued earlier.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02654990
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02654990