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Phase 2 N=248 Randomized Treatment

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

Multiple Myeloma

Enrolled (actual)
248
Serious AEs
49.8%
Results posted
Jul 2024
Primary outcome: Primary: Overall Response Rate (ORR) — 62.2; 65.1; 50.6 percentage of participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Panobinostat Capsules (Drug); Bortezomib Injection (Drug); Dexamethasone tablets (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
pharmaand GmbH
Primary completion
Oct 2019

Outcome Measures

OutcomeResultp-value
PRIMARY
Overall Response Rate (ORR)
62.2; 65.1; 50.6
SECONDARY
ORR Throughout the Study
62.2; 67.5; 53.0
SECONDARY
iCR Rate
3.7; 1.2; 1.2
SECONDARY
sCR Rate
1.2; 1.2; 3.6
SECONDARY
CR Rate
8.5; 8.4; 2.4
SECONDARY
VGPR Rate
19.5; 25.3; 20.5
SECONDARY
Progression-free Survival (PFS)
15; 13; 8
SECONDARY
Overall Survival (OS)
35; 32; 22
SECONDARY
Maximum Plasma Concentration (Cmax): Panobinostat
14.30; 14.12; 6.13
SECONDARY
Cmax: Bortezomib
16.67; 19.47; 18.29
SECONDARY
Time to Reach Cmax (Tmax): Panobinostat
1.93; 1.80; 1.82
SECONDARY
Tmax: Bortezomib
0.84; 0.77; 0.77
SECONDARY
Exposure Response: Cmax for Panobinostat
63.1; 62.2; 35.3; 32.2; 28.7; 21.7
SECONDARY
Change From Baseline in European Organization of Research and Treatment of Cancer (EORTC) Quality of Life Core 30-item Questionnaire (QLQ-C30) Global Health Status (GHS) Score
6.0; 0.0; -4.6
SECONDARY
Change From Baseline in the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group-Neurotoxicity (GOG-Ntx) Neurotoxicity Subscale Score
-3.6; -3.9; -0.1
SECONDARY
Time to Progression (TTP)
17; 13; 8
SECONDARY
Time to Response (TTR)
3; 3; 3
SECONDARY
Duration of Response (DOR)
22; 12; 10.429

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 3 different regimens of panobinostat (20 milligrams [mg] thrice a week [TIW], 20 mg twice a week [BIW], and 10 mg TIW) in combination with subcutaneous bortezomib and dexamethasone and to provide exposure, safety and efficacy data to identify the optimal regimen of panobinostat in a randomized, 3-arm parallel design. This study will also assess the impact of administering subcutaneous bortezomib (in combination with panobinostat and dexamethasone) twice weekly for 4 cycles, and then weekly starting from Cycle 5 until disease progression in participants ≤ 75 years of age. Participants > 75 years of age will receive subcutaneous bortezomib weekly for the entire treatment period (in combination with panobinostat and dexamethasone) until disease progression. Participants will be treated until disease progression or until they discontinue earlier due to unacceptable toxicity or for other reasons. Participants who discontinued study treatment for reasons other than disease progression will be followed for efficacy every 6 weeks. All participants will be followed for survival until the last participant entering long-term follow-up has completed a 3-year survival follow-up or discontinued earlier.

Eligibility Criteria

Inclusion Criteria

  • multiple myeloma per International Myeloma Working Group 2014 definition
  • requiring treatment for relapsed or relapsed/refractory disease
  • measurable disease based on central protein assessment
  • received 1 to 4 prior lines of therapy
  • prior immunomodulatory agent(s) exposure
  • acceptable lab values prior to randomization

Exclusion Criteria

  • primary refractory myeloma
  • refractory to bortezomib
  • concomitant anti-cancer therapy (other than bortezomib/dexamethasone and bisphosphonates)
  • prior treatment with pan-deacetylase inhibitors
  • clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months prior to randomization)
  • unresolved diarrhea ≥ Common Terminology Criteria for adverse events grade 2 or presence of medical condition associated with chronic diarrhea (such as irritable bowel syndrome and inflammatory bowel disease)

Other protocol-defined inclusion/exclusion criteria may apply.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02654990). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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