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

Novartis Pharmaceuticals

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Conditions

Multiple Myeloma

Interventions

panobinostat (capsules)DRUG

Panobinostat capsules, oral: 10mg, 15mg, 20mg dosing 3x a week, 1 week on / 1 week off, in a 4 week cycle (28 days). Treatment arm A: only capsules of 10mg will be used Treatment arm B: capsules of 10mg and 15mg are foreseen for dose reduction only.

carfilzomib (infusion)DRUG

Carfilzomib infusion; 20 mg/m2 i.v. on C1D1 and C1D2; 56 mg/m2 i.v. on subsequent dosing days (2x a week; 3 weeks on/1 weeks off ); 4 week cycle (28 days)

dexamethasone (tablets)DRUG

Dexamethasone tablets p.o. 20 mg on days of carfilzomib infusion (2x week) and on D22 and D23 of each 4 week cycle (28 days)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Overall response rate (ORR) using investigator's response assessment

The primary endpoint if Overall Response Rate (ORR) using investigator response assessment according to IMWG criteria. The analysis of ORR will be performed after all randomized patients have completed 6 months of study treatment or discontinued treatment earlier.