Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

— PANORAMA_3  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02654990
• Other study ID #: CLBH589D2222
• Secondary ID: 2015-001564-19
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2016
• Est. completion date: August 15, 2022

Study information

• Verified date: December 2023
• Source: pharmaand GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 249
• Est. completion date: August 15, 2022
• Est. primary completion date: October 18, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• panobinostat capsules
20mg, 10mg or 15mg (for dose reductions only)
• 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
• dexamethasone tablets
pre and 24h after BTZ administration; patients = 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Prahran	Victoria
Belgium	Novartis Investigative Site	Hasselt
Brazil	Novartis Investigative Site	Barretos	Sao Paulo
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	Sao Paulo
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Kitchener	Ontario
Czechia	Novartis Investigative Site	Ostrava Poruba	Czech Republic
Czechia	Novartis Investigative Site	Praha
France	Novartis Investigative Site	Avignon Cedex 9
France	Novartis Investigative Site	Bayonne	Bayonne Cedex
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	La Roche sur Yon Cedex
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Metz
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Pessac
Germany	Novartis Investigative Site	Bad Saarow
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Halle Saale
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Leipzig
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Patras
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen	HUN
Hungary	Novartis Investigative Site	Kaposvar
Hungary	Novartis Investigative Site	Nyiregyhaza
Italy	Novartis Investigative Site	Rimini	RN
Italy	Novartis Investigative Site	Roma	RM
Korea, Republic of	Novartis Investigative Site	Hwasun
Korea, Republic of	Novartis Investigative Site	Seoul
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Beirut
Lebanon	Novartis Investigative Site	Sidon
Netherlands	VUmc, Hematology, PK2 BR012	Amsterdam
Netherlands	Albert Schweitzer ziekenhuis, Hematology	Dordrecht
Norway	Novartis Investigative Site	Oslo
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Torun
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Porto
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saratov
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	L'Hospitalet De Llobregat	Catalunya
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Lulea
Sweden	Novartis Investigative Site	Lund
Sweden	Novartis Investigative Site	Uppsala
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Mueang Nonthaburi	Muang
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Fayetteville	Arkansas
United States	Novartis Investigative Site	Fort Collins	Colorado
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Lake Success	New York
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Morgantown	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
pharmaand GmbH

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR) up to 8 cycles	assessed according to IMWG guidelines	up to 8 cycles per patient, approximately 30 months
Secondary	ORR throughout study		approximately 70 months
Secondary	individual immunophenotypic complete response (CR) rate		approximately 30 and 70 months
Secondary	Progression-free survival		approximately 30 and 70 months
Secondary	Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ)		approximately 30 months
Secondary	Time to progression		approximately 30 and 70 months
Secondary	Time to response		approximately 30 and 70 months
Secondary	Duration of response (DOR)		approximately 30 and 70 months
Secondary	European Organization of Research and Treatment of Cancer Quality of Life core 30-item questionnaire scores over time compared	EORTC QLQ-C30 on-treatment and in post treatment follow-up	approximately 30 and 70 months
Secondary	individual stringent CR rate		approximately 30 and 70 months
Secondary	individual CR rate		approximately 30 and 70 months
Secondary	overall survival		approximately 30 and 70 months
Secondary	individual Very Good Partial Response rate		approximately 30 and 70 months
Secondary	Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time	FACT/GOG-Ntx on-treatment	approximately 30 and 70 months
Secondary	Time to reach Cmax for PAN and BTZ		approximately 30 months
Secondary	Minimum observed plasma concentration (Cmin) for PAN and BTZ		approximately 30 months
Secondary	Observed plasma concentration 24 hours after single and multiple dose administration of PAN and BTZ		24 hours after every dose, approximately 30 months