Clinical trial NCT02756663: Panobinostat in Combination With Carfilzomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
Official title: A Randomized, Triple-arm, Controlled, Open-label, Multicenter Phase II Study Assessing Two Different Doses of Panobinostat in Combination With Carfilzomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: multiple myeloma
MM
relapsed
relapsed and refractory
panobinostat
LBH589
histone deacetylase inhibitor
carfilzomib
proteasome inhibitor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-04-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the anti-myeloma effect of panobinostat given at two different doses (10 mg and 20 mg oral) in combination with carfilzomib (20/56 mg/m2 i.v.) and low dose dexamethasone (20 mg oral) vs carfilzomib plus low-dose dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma. Safety and efficacy will be evaluated. Treatment will be administered in 4-week cycles until patients discontinue due to disease progression or unacceptable toxicity or for other reasons.

Patients who discontinue the study treatment for reasons other than documented disease progression will be followed for disease assessments every 8 weeks until progression. All patients will be followed for survival until 3 years have passed from their entry into the study, or they have discontinued the follow up earlier.


Eligibility criteria: Inclusion Criteria:

* Previous diagnosis of MM based on IMWG definitions (Rajkumar, 2014)
* Prior treatment with 1 to 3 prior lines of therapy
* Relapsed or relapsed and refractory MM
* Measureable disease at screening based on central laboratory assessment
* ECOG Performance status ≤ 2
* Acceptable lab values prior to starting study treatment

Exclusion Criteria:

* Primary refractory myeloma
* Prior treatment with DAC inhibitors including panobinostat
* Prior treatment with carfilzomib
* Allogeneic stem cell transplant recipient with graft versus host disease (either active or requiring immunosuppression)
* Any concomitant anti-cancer therapy besides the study treatment (bisphosphonates are permitted only if commenced prior to the start of screening period)
* Intolerance to dexamethasone or contraindication to carfilzomib or dexamethasone
* Unresolved diarrhea ≥ CTCAE grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease)

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Overall response rate (ORR) using investigator's response assessment
timeFrame: All patients treated for 6 cycles (cycle=28 days)
Secondary outcomes:
measure: Very Good Partial Response (VGPR) or better as best response using investigator response assessment based on International Myeloma Working Group (IMWG) criteria
timeFrame: All patients treated for 6 cycles (cycle=28 days)
measure: Progression-free survival (PFS) using investigator's response assessment based on IMWG criteria
timeFrame: All patients treated for 6 cycles (cycle=28 days)
measure: Overall survival (OS)
timeFrame: All patients treated for 6 cycles (cycle=28 days)
measure: Time to response (TTR) using investigator's response assessment based on IMWG criteria
timeFrame: All patients treated for 6 cycles (cycle=28 days)
measure: Duration of Response (DOR) using investigator's response assessment based on IMWG criteria
timeFrame: All patients treated for 6 cycles (cycle = 28 days)
measure: Time to progression (TTP) using investigator's response assessment based on IMWG criteria
timeFrame: All patients treated for 6 cycles (cycle = 28 days)
measure: Time to reach Cmax for panobinostat (PAN) and carfilzomib (CFZ)
timeFrame: All patients treated for 6 cycles (cycle=28 days);
measure: Minimum observed plasma concentration (Cmin) for carfilzomib
timeFrame: All patients treated for 6 cycles (cycle=28 days)
measure: Concentration of panobinostat in blood plasma in 48 hrs after the dose.
timeFrame: All patients treated for 6 cycles (cycle = 28 days)
measure: Total carfilzomib exposure over time in blood plasma .
timeFrame: All patients treated for 6 cycles (cycle=28 days)
measure: Health related quality of life (HRQoL) change over time measured by EORTC questionnaire QLQ-C30 and QLQ-MY20 for disease symptoms
timeFrame: All patients treated for 6 cycles (cycle=28 days)
Other outcomes:
Locations:
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: