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

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ClinicalTrials.gov Identifier: NCT02654990
Recruitment Status : Recruiting
First Posted : January 13, 2016
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE December 16, 2015
First Posted Date  ICMJE January 13, 2016
Last Update Posted Date March 5, 2019
Actual Study Start Date  ICMJE April 27, 2016
Estimated Primary Completion Date June 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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
Change History Complete list of historical versions of study NCT02654990 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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 Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Panobinostat/Bortezomib/Dexamethasone in Relapsed or Relapsed-and-refractory Multiple Myeloma
Official Title  ICMJE 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

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  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: panobinostat capsules
    20mg, 10mg or 15mg (for dose reductions only)
    Other Name: PAN, LBH589
  • Drug: bortezomib injection
    1.3mg/m2 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/1week 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 * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 11, 2016)
240
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date December 15, 2022
Estimated Primary Completion Date June 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 then 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  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Listed Location Countries  ICMJE 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  ICMJE NCT02654990
Other Study ID Numbers  ICMJE CLBH589D2222
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
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP