Phase II Study to Evaluate Fenofibrate Therapy in Patients With Smoldering or Symptomatic Multiple Myeloma

NCT01965834 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 20110069
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple myeloma cells are dependent on calcium (Ca2+) for their function. Specifically, Ca2+ is required for the function of the endoplasmic reticulum in which proteins, including immunoglobulins, are folded prior to their release from the cell. Multiple myeloma cells secrete large concentrations of immunoglobulins continuously and as result depend on mitochondria activity to replenish the Ca2+ levels in the endoplasmic reticulum as was shown in vitro in our lab. Fenofibrate has been shown to inhibit mitochondrial function resulting in inhibition of protein folding in the endoplasmic reticulum of multiple myeloma (MM) cells that leads to the induction of a stress signal known as the unfolded protein response and subsequently apoptosis. The effective anti-myeloma concentrations for fenofibrate are attainable in the clinical setting as they are in the same range as the effective concentrations for anti-hyperlipidemic effect. The investigators propose to evaluate fenofibrate therapy in multiple myeloma patients.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Fenofibrate

Outcome Measures

Primary Outcomes (1)

• Rate of Response in Participants Receiving Fenofibrate Therapy

  To determine response rate (Strict Complete Response (sCR), Complete response (CR), Very Good Partial Response (VgPR), and Partial Response (PR)) in multiple myeloma patients receiving oral fenofibrate therapy. Response will be measured by serum and urine protein electrophoresis and immunofixation, as well as by percentage of plasma cells present on bone marrow biopsy.

  After two cycles, about 2 months

Secondary Outcomes (2)

• Number of Subjects Experiencing Adverse Events

  Up to 8 months

• Proportion of Participants Achieving Progression-Free Survival

  6 months, 12 months

Study Arms (1)

Fenofibrate Therapy

EXPERIMENTAL

Fenofibrate orally daily for each 28 day cycle, per study protocol.

Drug: Fenofibrate

Interventions

Fenofibrate DRUG

Upon screening, registration and enrollment, all subjects will receive Fenofibrate 160 mg orally daily for at least 2 months and may continue receiving study medication for as long as in the opinion of the investigator there is clinical benefit in doing so. Patients with calculated creatinine clearance \< 50 mL/min will receive a reduced dose of 54 mg orally daily.

Also known as: Fenofibric acid

Fenofibrate Therapy

Eligibility Criteria

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

You may qualify if:

• Patient must have histologically or cytologically confirmed multiple myeloma (smoldering myeloma and symptomatic multiple myeloma).
• Patients must have measurable disease and therefore must have at least one of the following:
• Serum M-protein ≥ 1 gm/dL (≥ 10 gm/L)
• Urine M-protein ≥ 200 mg/24 hr
• Serum free light chain (FLC) assay: involved FLC ≥ 10 mg/dL (≥ 100 mg/L) provided serum FLC ratio is abnormal.
• Male or female ≥ 18 years of age.
• Life expectancy of ≥ 6 months.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Normal organ and marrow function as defined below:
• Absolute Neutrophil Count (ANC) ≥ 1,000/mm\^3
• Platelets ≥75,000/mm\^3
• Hemoglobin ≥ 8 g/dL
• Calculated serum creatinine (calculated by Cockcroft-Gault method) ≥ 30 mL/min
• Aspartate transaminase (AST)/serum glutamic oxaloacetic transaminase (SGOT)/ Alanine transaminase (ALT)/serum glutamate-pyruvate transaminase (SGPT) ≤ 2.5 X upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 X ULN

You may not qualify if:

• Patients who only present with isolated plasmacytomas
• Inability to swallow oral medication.
• Prior allogeneic stem cell transplant (subject with prior autologous transplant is eligible).
• Patient has plans to undergo any type of stem cell transplantation (allogeneic or autologous) within 4 weeks of initiation of study therapy.
• Concurrent therapy with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) Reductase Inhibitors.
• Patient with gallbladder disease or cholelithiasis.
• Patient has active liver disease, including biliary cirrhosis and unexplained liver function abnormalities.
• Patients receiving renal dialysis.
• History of hypersensitivity to fenofibrate or fenofibric acid, including sever skin rashes (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Patients who would be receiving any other investigational agents while on study.
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient has systemic infection requiring treatment.
• Patient has acute diffuse infiltrative pulmonary disease or pericardial disease.
• Subject is receiving corticosteroid therapy (\> 10 mg of prednisone or equivalent).

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Fenofibrate; fenofibric acid

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)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Phenyl Ethers; Ethers; Benzophenones; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Ketones

Results Point of Contact

• Title: Denise Pereira MD
• Organization: University of Miami

dpereira2@med.miami.edu

305-243-4909

Study Officials

• Denise Pereria, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Study Record Dates

• First Submitted: October 15, 2013
• First Posted: October 18, 2013
• Study Start: November 19, 2012
• Primary Completion: March 21, 2016
• Study Completion: July 1, 2016
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)