Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma (PANORAMA_3)

• ClinicalTrials.gov Identifier: NCT02654990
• Recruitment Status: Completed
• First Posted: January 13, 2016
• Last Update Posted: December 22, 2023
• Sponsor: pharmaand GmbH
• Information provided by (Responsible Party): pharmaand GmbH

Tracking Information

• First Submitted Date: December 16, 2015
• First Posted Date: January 13, 2016
• Last Update Posted Date: December 22, 2023
• Actual Study Start Date: April 27, 2016
• Actual Primary Completion Date: October 18, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 13, 2016)

Overall response rate (ORR) up to 8 cycles [ Time Frame: up to 8 cycles per patient, approximately 30 months ]

assessed according to IMWG guidelines

Original Primary Outcome Measures (submitted: January 11, 2016)

Overall response rate (ORR) up to 8 cycles [ Time Frame: up to 8 cycles per patient, approximately after 30 months ]

assessed according to IMWG guidelines

Current Secondary Outcome Measures (submitted: January 3, 2018)

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

Original Secondary Outcome Measures (submitted: January 11, 2016)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma
• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: panobinostat capsules
  20mg, 10mg or 15mg (for dose reductions only)
  Other Name: PAN, LBH589
• Drug: 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
  Other Name: BTZ
• Drug: dexamethasone tablets
  pre and 24h after BTZ administration; patients ≤ 75 years at time of screening: 20mg/dose patients > 75 years: 10mg/dose
  Other Name: Dex

Study Arms

• 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
  Interventions:

  • Drug: panobinostat capsules
  • Drug: bortezomib injection
  • Drug: dexamethasone tablets
• 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
  Interventions:

  • Drug: panobinostat capsules
  • Drug: bortezomib injection
  • Drug: dexamethasone tablets
• 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
  Interventions:

  • Drug: panobinostat capsules
  • Drug: bortezomib injection
  • Drug: dexamethasone tablets

• Publications *: Laubach JP, Schjesvold F, Mariz M, Dimopoulos MA, Lech-Maranda E, Spicka I, Hungria VTM, Shelekhova T, Abdo A, Jacobasch L, Polprasert C, Hajek R, Illes A, Wrobel T, Sureda A, Beksac M, Goncalves IZ, Blade J, Rajkumar SV, Chari A, Lonial S, Spencer A, Maison-Blanche P, Moreau P, San-Miguel JF, Richardson PG. Efficacy and safety of oral panobinostat plus subcutaneous bortezomib and oral dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 3): an open-label, randomised, phase 2 study. Lancet Oncol. 2021 Jan;22(1):142-154. doi: 10.1016/S1470-2045(20)30680-X. Epub 2020 Dec 7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 5, 2019): 249
• Original Estimated Enrollment (submitted: January 11, 2016): 240
• Actual Study Completion Date: August 15, 2022
• Actual Primary Completion Date: October 18, 2019 (Final data collection date for primary outcome measure)

Eligibility 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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Brazil, Canada, Czechia, France, Germany, Greece, Hungary, Italy, Korea, Republic of, Lebanon, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Sweden, Thailand, Turkey, United States
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT02654990
• Other Study ID Numbers: CLBH589D2222; 2015-001564-19 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: pharmaand GmbH
• Original Responsible Party: Novartis Pharmaceuticals
• Current Study Sponsor: pharmaand GmbH
• Original Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: pharmaand GmbH
• Verification Date: December 2023