Clinical Trials /

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

NCT02654990

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CLBH589D2222
  • NCT ID: NCT02654990

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
panobinostat capsulesPAN, LBH589Arm A - 20mg PAN TIW
bortezomib injectionBTZArm A - 20mg PAN TIW
dexamethasone tabletsDexArm A - 20mg PAN TIW

Purpose

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 Arms

NameTypeDescriptionInterventions
Arm A - 20mg PAN TIWExperimental20mg panobinostat three times a week, 2 weeks on/1week of in combination with s.c. bortezomib and p.o. dexamethasone
  • panobinostat capsules
  • bortezomib injection
  • dexamethasone tablets
Arm B - 20mg PAN BIWExperimental20mg panobinostat twice a week, 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
  • panobinostat capsules
  • bortezomib injection
  • dexamethasone tablets
Arm C - 10mg PAN TIWExperimental10mg panobinostat three times a week 2 weeks on/1 week off in combination with s.c. bortezomib and p.o. dexamethasone
  • panobinostat capsules
  • bortezomib injection
  • dexamethasone tablets

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 3 prior lines of therapy

          -  prior IMiD exposure

          -  acceptable lab values prior to starting study treatment

        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 month prior to screening)

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR) up to 8 cycles
Time Frame:up to 8 cycles per patient, approximately 30 months
Safety Issue:
Description:assessed according to IMWG guidelines

Secondary Outcome Measures

Measure:ORR throughout study
Time Frame:approximately 70 months
Safety Issue:
Description:
Measure:individual immunophenotypic complete response (CR) rate
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:Progression-free survival
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:Maximum plasma concentration (Cmax) for panobinostat (PAN) and bortezomib (BTZ)
Time Frame:approximately 30 months
Safety Issue:
Description:
Measure:Time to progression
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:Time to response
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:Duration of response (DOR)
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:EORTC QLQ-C30 on-treatment and in post treatment follow-up
Measure:individual stringent CR rate
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:individual CR rate
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:overall survival
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:individual Very Good Partial Response rate
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:
Measure:Functional Assessment of Cancer Therapy / Gynecologic Oncology Group - Neurotoxicity scale scores over time
Time Frame:approximately 30 and 70 months
Safety Issue:
Description:FACT/GOG-Ntx on-treatment
Measure:Time to reach Cmax for PAN and BTZ
Time Frame:approximately 30 months
Safety Issue:
Description:
Measure:Minimum observed plasma concentration (Cmin) for BTZ
Time Frame:approximately 30 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • multiple myeloma
  • relapsed or relapsed/refractory
  • LBH589
  • panobinostat
  • bortezomib
  • dexamethasone

Last Updated

February 23, 2017