Panobinostat in Combination With Carfilzomib and Dexamethasone in Relapsed or Relapsed and Refractory Multiple Myeloma

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

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.

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.