Prospective Observation of Cardiac Safety With Proteasome Inhibition (PROTECT)

The purpose of this study is to better define and understand potential cardiac toxicities of proteasome inhibitors and to understand optimal management strategies to treat and prevent cardiovascular events.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Multiple Myeloma

Detailed Description

Cancer treatments, using proteasome inhibitors, have the potential in induce cardiac toxicities including heart failure (HF), hypertension, arrhythmias and ischemic heart disease. While the presence of cardiac events may be a class effect of proteasome inhibitors (PI), the effect may be more profound with the irreversible inhibition of carfilzomib compared with reversible inhibition with bortezomib. Data available from currently published clinical trials may be inadequate to fully understand the incidence and severity of cardiac injury in patients treated with proteasome inhibitors because the trials were not designed to fully assess cardiac events. The purpose of this study is to better define and understand potential cardiac toxicity and begin to understand optimal management strategies.

• Study Type: Observational
• Enrollment (Actual): 95

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-5159
      • University of Pennsylvania/Smilow Center for Translational Research
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Multiple Myeloma patients being treated with bortezomib or carfilzomib, per oncology physician decision.

Description

Inclusion Criteria:

• Relapsed multiple myeloma at any time-point in treatment course and planning to start a proteasome inhibitor-based therapy as part of standard care
• Received at least one prior line of therapy for multiple myeloma (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as one line of therapy)
• Males and females ≥ 18 years of age
• Able to provide written informed consent in accordance with federal, local, and institutional guidelines

Exclusion Criteria:

• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Known or suspected AL amyloidosis, secondary amyloidosis or cardiac amyloidosis
• Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
• Waldenström Macroglobulinemia
• Myelodysplastic syndrome
• History of MI within the last 3 months
• Symptomatic unstable cardiac arrhythmia requiring treatment in the past 3 months
• Class 3 or 4 New York Heart Association Heart Failure in the past 3 months
• Any other clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Multiple Myeloma (MM) treatment with bortezomib; No intervention planned.
Multiple Myeloma (MM) treatment with carfilzomib; No intervention planned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of cardiac events of patients receiving PIs for MM.	18 months

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Takeda
• Investigators: Principal Investigator: Robert F Cornell, MD, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• Cornell RF, Ky B, Weiss BM, Dahm CN, Gupta DK, Du L, Carver JR, Cohen AD, Engelhardt BG, Garfall AL, Goodman SA, Harrell SL, Kassim AA, Jadhav T, Jagasia M, Moslehi J, O'Quinn R, Savona MR, Slosky D, Smith A, Stadtmauer EA, Vogl DT, Waxman A, Lenihan D. Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma. J Clin Oncol. 2019 Aug 1;37(22):1946-1955. doi: 10.1200/JCO.19.00231. Epub 2019 Jun 12.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2014
• Primary Completion (Actual): July 15, 2019
• Study Completion (Actual): July 15, 2019

Study Registration Dates

• First Submitted: June 26, 2014
• First Submitted That Met QC Criteria: June 26, 2014
• First Posted (Estimate): July 1, 2014

Study Record Updates

• Last Update Posted (Actual): September 14, 2020
• Last Update Submitted That Met QC Criteria: September 10, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Heart Failure; Multiple Myeloma; Carfilzomib; Bortezomib; Cardiac Toxicity
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Heart Failure; Multiple Myeloma
• Other Study ID Numbers: 140404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There are no plans to share individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No