Study of the Combination of Panobinostat & Carfilzomib in Patients With Relapsed &/or Refractory Multiple Myeloma

NCT01549431 | Completed Phase 1 DMC

• 2 other identifiers: IRB00049368WCI2011-11/MMRC036
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, the combination of panobinostat and carfilzomib have on the patient's cancer. It will determine the side effects of different dose levels of panobinostat and carfilzomib and determine the best dose and schedule of the two drugs to recommend for future studies. The study will assess the effects of the drug on multiple myeloma. In addition, tests to study the way the drugs work will also be done. The combination of the 2 drug classes have shown both pre-clinical (studies done in the lab) and clinical (studies done with people) effects against multiple myeloma. For this reason, these 2 drugs are being studied in combination to determine the side effects and anti-myeloma effects of the 2 drugs.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of the combination of panobinostat and carfilzomib

  28 day cycle

Study Arms (1)

Combo of Panobinostat and Carfilzomib

EXPERIMENTAL

A cycle of therapy is 4 weeks (28 days in duration). Carfilzomib (with dexamethasone during cycle 1) will be administered intravenously infusion on days 1, 2 and 8, 9 and 15, 16 of every 28 day cycle. Panobinostat is administered orally three times per week.

Drug: Panobinostat; Drug: Carfilzomib; Drug: Dexamethasone

Interventions

Panobinostat DRUG

Panobinostat will be supplied as 5-mg or 20-mg pink/opaque-colored, hard gelatin capsules. Panobinostat is administered orally three times per week. * Standard 3+3 design * 3 out of 4 weeks

Also known as: LBH589

Combo of Panobinostat and Carfilzomib

Carfilzomib DRUG

Carfilzomib in Cycle 1 will be initiated intravenously at 20 mg/m² on Days 1 and 2 and escalated to 27 mg/m² for Days 8, 9, 15, and 16 of Cycle 1 and for the duration of treatment. * Standard 3+3 design * Days 1/2, 8/9 and 15/16 every 4 weeks

Also known as: Kyprolis

Combo of Panobinostat and Carfilzomib

Dexamethasone DRUG

Dexamethasone (4 mg) must be given prior to each carfilzomib infusion during Cycle 1. Dexamethasone pre-dose should continue through Cycle 2 if fever is observed post-dose, Cycle 2 Day 1, or thereafter associated with the infusion of carfilzomib.

Also known as: Decadron

Combo of Panobinostat and Carfilzomib

Eligibility Criteria

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

You may qualify if:

• Male or female patients aged ≥ 18 years old
• Diagnosis of multiple myeloma (MM) following at least one prior therapy; there is no maximum number or prior therapies
• Patients must have relapsed/ refractory disease and be in need of therapy with evidence of measurable disease defined as at least one of the following:
• Serum M protein ≥ 0.5 g/dl (≥ 5g/l)
• Urine M protein ≥ 200 mg/24 hours
• Serum free light chain (FLC) assay: Involved FLC assay ≥ 10 mg/dl (≥100 mg/l) and an abnormal serum free light chain ratio (\< 0.26 or \> 1.65)
• Measurable plasmacytoma (Prior biopsy is acceptable)
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Patients must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1.0 x 10⁹/L (growth factors cannot be used within 3 days of screening)
• Hemoglobin ≥ 8 g/dl (PRBC transfusions cannot be used within 3 days of screening)
• Platelets ≥ 75 x 10⁹/L (platelet transfusions cannot be used within 3 days of screening)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Serum bilirubin ≤ 1.5 x ULN
• Serum potassium ≥ lower limit of normal (LLN)

You may not qualify if:

• Prior histone deacetylase (HDAC), dichloroacetate (DAC), or valproic acid for the treatment of cancer
• Prior treatment with carfilzomib
• Daily requirement for corticosteroids \> prednisone 10 mg/day or equivalent
• Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
• History or presence of sustained ventricular tachyarrhythmia. (Patients with a history of atrial arrhythmia are eligible but should be discussed with the Principal Investigator prior to enrollment)
• History of congenital long QT syndrome
• Any history of ventricular fibrillation or torsade de pointes
• Bradycardia defined as heart rate (HR) \< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50 bpm.
• ECG evidence of acute ischemia or grade 3 conduction system abnormalities (unless subject has a pacemaker)
• Screening ECG with a corrected QT interval (QTc) \> 450 msec
• Right bundle branch block + left anterior hemiblock (bifascicular block)
• Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting study drug
• Other clinically significant heart disease (e.g., congestive heart failure \[CHF\] New York Heart Association class III or IV, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) (Patients with a history of atrial arrhythmias may be eligible if they are controlled and approved by the Lead Principal Investigator)
• Impairment of GI function or GI disease that may significantly alter the absorption of panobinostat. Inability to take oral medications, requirement for IV alimentation, active peptic ulcer disease or prior surgical procedures or bowel resection affecting absorption of oral medications.

Sponsors & Collaborators

• Emory University: lead
• Multiple Myeloma Research Consortium: collaborator
• Novartis: collaborator
• Onyx Therapeutics, Inc.: collaborator
• Amgen: collaborator
• University of California, San Francisco: collaborator
• University of Chicago: collaborator

Study Sites (3)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Related Publications (1)

• Kaufman JL, Mina R, Jakubowiak AJ, Zimmerman TL, Wolf JJ, Lewis C, Gleason C, Sharp C, Martin T, Heffner LT, Nooka AK, Harvey RD, Lonial S. Combining carfilzomib and panobinostat to treat relapsed/refractory multiple myeloma: results of a Multiple Myeloma Research Consortium Phase I Study. Blood Cancer J. 2019 Jan 4;9(1):3. doi: 10.1038/s41408-018-0154-8.

  PMID: 30610196 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Panobinostat; carfilzomib; Dexamethasone; Calcium Dobesilate

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

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Jonathan Kaufman, MD

  Emory University Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 7, 2012
• First Posted: March 9, 2012
• Study Start: January 1, 2012
• Primary Completion: February 1, 2016
• Study Completion: April 1, 2017
• Last Updated: January 16, 2019

Record last verified: 2019-01

Locations

US (3)