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

NCT ID: NCT02756663

Last Updated: 2016-11-08

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2021-02-28

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.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; MM; relapsed; relapsed and refractory; panobinostat; LBH589; histone deacetylase inhibitor; carfilzomib; proteasome inhibitor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: PAN (10mg) + CFZ + Dex

Panobinostat (PAN) 10mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle

Group Type: EXPERIMENTAL

panobinostat (capsules)

Intervention Type: 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)

Intervention Type: 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)

Intervention Type: 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)

Arm B: PAN (20mg) + CFZ + Dex

Panobinostat (PAN) 20mg orally, combined with carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle

Group Type: EXPERIMENTAL

panobinostat (capsules)

Intervention Type: 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)

Intervention Type: 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)

Intervention Type: 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)

Arm C: CFZ + Dex

Carfilzomib (CFZ) 20/56 mg/m2 i.v. and dexamethasone (Dex) 20mg orally, in 4 week cycle

Group Type: ACTIVE_COMPARATOR

carfilzomib (infusion)

Intervention Type: 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)

Intervention Type: 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)

Interventions

panobinostat (capsules)

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.

Intervention Type: DRUG

carfilzomib (infusion)

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)

Intervention Type: DRUG

dexamethasone (tablets)

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)

Intervention Type: DRUG

Other Intervention Names

PAN, LBH589; CFZ; Dex

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Other Identifiers

CLBH589X2201

Identifier Type: -

Identifier Source: org_study_id