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.
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
Interventions
Drug | Synonyms | Arms |
---|
panobinostat capsules | PAN, LBH589 | Arm A - 20mg PAN TIW |
bortezomib injection | BTZ | Arm A - 20mg PAN TIW |
dexamethasone tablets | Dex | Arm 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
Name | Type | Description | Interventions |
---|
Arm A - 20mg PAN TIW | Experimental | 20mg 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 BIW | Experimental | 20mg 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 TIW | Experimental | 10mg 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 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.
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 PAN and 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: | Active, not recruiting |
Lead Sponsor: | SecuraBio |
Trial Keywords
- multiple myeloma
- relapsed or relapsed/refractory
- LBH589
- panobinostat
- bortezomib
- dexamethasone
Last Updated
March 19, 2021