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

NCT02756663 | Withdrawn Phase 2 DMC

• 1 other identifier: CLBH589X2201
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• 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.

  All patients treated for 6 cycles (cycle=28 days)

Secondary Outcomes (11)

• Very Good Partial Response (VGPR) or better as best response using investigator response assessment based on International Myeloma Working Group (IMWG) criteria

  All patients treated for 6 cycles (cycle=28 days)

• Progression-free survival (PFS) using investigator's response assessment based on IMWG criteria

  All patients treated for 6 cycles (cycle=28 days)

• Overall survival (OS)

  All patients treated for 6 cycles (cycle=28 days)

• Time to response (TTR) using investigator's response assessment based on IMWG criteria

  All patients treated for 6 cycles (cycle=28 days)

• Duration of Response (DOR) using investigator's response assessment based on IMWG criteria

  All patients treated for 6 cycles (cycle = 28 days)

Study Arms (3)

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

EXPERIMENTAL

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

Drug: panobinostat (capsules); Drug: carfilzomib (infusion); Drug: dexamethasone (tablets)

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

EXPERIMENTAL

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

Drug: panobinostat (capsules); Drug: carfilzomib (infusion); Drug: dexamethasone (tablets)

Arm C: CFZ + Dex

ACTIVE COMPARATOR

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

Drug: carfilzomib (infusion); Drug: dexamethasone (tablets)

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.

Also known as: PAN, LBH589

Arm A: PAN (10mg) + CFZ + Dex; Arm B: PAN (20mg) + CFZ + Dex

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)

Also known as: CFZ

Arm A: PAN (10mg) + CFZ + Dex; Arm B: PAN (20mg) + CFZ + Dex; Arm C: CFZ + Dex

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)

Also known as: Dex

Arm A: PAN (10mg) + CFZ + Dex; Arm B: PAN (20mg) + CFZ + Dex; Arm C: CFZ + Dex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Panobinostat; Capsules; carfilzomib; Dexamethasone; Tablets

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2016
• First Posted: April 29, 2016
• Study Start: December 1, 2016
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2021
• Last Updated: November 8, 2016

Record last verified: 2016-11