Clinical trial NCT02178579: Prospective Observation of Cardiac Safety With Proteasome Inhibition
Official title: Prospective Observation of Cardiac Safety With Proteasome Inhibition
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Multiple Myeloma
Keywords: Heart Failure
Cardiac Toxicity
Multiple Myeloma
Bortezomib
Carfilzomib
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Takeda
First posted: 2014-07-01
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Multiple Myeloma patients being treated with bortezomib or carfilzomib, per oncology physician decision.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of cardiac events of patients receiving PIs for MM.
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania/Smilow Center for Translational Research
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Robert F Cornell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.