Fluoroquinolone Resistance Prevalence Study

Multiple Myeloma Clinical Trial

— FRE  

Official title:

Exploratory Study of Fluoroquinolone Resistance for Patients Undergoing Autologous Hematopoietic Stem Cell (HSC) Transplantation in the Treatment of Multiple Myeloma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05824689
• Other study ID #: 2021-1263
• Status: Recruiting
• Start date: July 8, 2022
• Est. completion date: April 2025

Study information

• Verified date: February 2024
• Source: Hackensack Meridian Health
• Contact: Mariefel Vendivil, RN
• Phone: 551-996-5828
• Email: Mariefel.Vendivil[@]hmhn.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an exploratory study to determine the prevalence of fluoroquinolone resistance in patients receiving dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation in the treatment of multiple myeloma (MM). These data may be used in subsequent studies exploring the use of prophylaxis in this patient population.

Description:

The goal of this observational study is to determine the prevalence of fluoroquinolone resistance in patients receiving dose-intense melphalan with autologous peripheral blood stem cell (PBSC) transplantation in the treatment of multiple myeloma (MM). The main question[s] it aims to answer are: - What is the prevalence of fluoroquinolone-resistant Enterobacterales (FRE) in patients undergoing autologous PBSC transplantation with dose-intense melphalan? - Does the risk of febrile neutropenia differ in FRE carriers compared to non-carriers? Participants will be tested for the presence of FRE before receiving fluoroquinolone prophylaxis at multiple points during the transplant course, including before chemotherapy mobilization (if used) using fluoroquinolone prophylaxis, at initial transplant hospitalization, at time of hospital discharge, and at or after day 84 after transplantation (day 0 is defined as day of HSC (hematopoietic stem cell) infusion). FRE colonization will not be a determining factor in the use of fluoroquinolone prophylaxis during the treatment course. This study will be open at two transplant units: Hackensack University Medical Center (HUMC) and MedStar Georgetown University Hospital (MGUH). Estimated number of subjects to be enrolled; - HUMC: 124 - MGUH: 20 Anticipated enrollment period: 12-months with monitoring of subjects for 84 days (twelve weeks) after transplantation. Data will be analyzed over a three-month period (total study period of 18 months).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 144
• Est. completion date: April 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects >18 yrs of age.
• Diagnosis of multiple myeloma undergoing (first or subsequent) autologous PBSC transplantation.
• Transplant conditioning with melphalan 200 mg/m2.
• PBSC cell dose of >2x10e6 CD34+ cells/kg.
• Able to receive fluoroquinolone prophylaxis.
• Subjects must give consent for enrollment into this study.

Exclusion Criteria:

• Unwillingness to provide informed consent.
• Enrollment into a treatment protocol prescribing antibiotic prophylaxis.
• A diagnosis other than multiple myeloma.
• Receiving a conditioning regimen other than melphalan 200 mg/m2.
• Known light-chain amyloid deposition in any organ.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Locations

Country	Name	City	State
United States	John Theurer Cancer Center, Hackensack Meridian Health	Hackensack	New Jersey
United States	Lombardi Comprehensive Cancer Center, Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hackensack Meridian Health

Country where clinical trial is conducted

United States, 

References & Publications (28)

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Innes AJ, Mullish BH, Ghani R, Szydlo RM, Apperley JF, Olavarria E, Palanicawandar R, Kanfer EJ, Milojkovic D, McDonald JAK, Brannigan ET, Thursz MR, Williams HRT, Davies FJ, Marchesi JR, Pavlu J. Fecal Microbiota Transplant Mitigates Adverse Outcomes Seen in Patients Colonized With Multidrug-Resistant Organisms Undergoing Allogeneic Hematopoietic Cell Transplantation. Front Cell Infect Microbiol. 2021 Aug 27;11:684659. doi: 10.3389/fcimb.2021.684659. eCollection 2021. — View Citation

Jernigan JA, Hatfield KM, Wolford H, Nelson RE, Olubajo B, Reddy SC, McCarthy N, Paul P, McDonald LC, Kallen A, Fiore A, Craig M, Baggs J. Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012-2017. N Engl J Med. 2020 Apr 2;382(14):1309-1319. doi: 10.1056/NEJMoa1914433. — View Citation

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Liao C, Taylor BP, Ceccarani C, Fontana E, Amoretti LA, Wright RJ, Gomes ALC, Peled JU, Taur Y, Perales MA, van den Brink MRM, Littmann E, Pamer EG, Schluter J, Xavier JB. Compilation of longitudinal microbiota data and hospitalome from hematopoietic cell transplantation patients. Sci Data. 2021 Mar 2;8(1):71. doi: 10.1038/s41597-021-00860-8. Erratum In: Sci Data. 2021 Apr 23;8(1):119. — View Citation

Maiolino A, Biasoli I, Lima J, Portugal AC, Pulcheri W, Nucci M. Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria. Bone Marrow Transplant. 2003 Mar;31(5):393-7. doi: 10.1038/sj.bmt.1703855. — View Citation

Peled JU, Devlin SM, Staffas A, Lumish M, Khanin R, Littmann ER, Ling L, Kosuri S, Maloy M, Slingerland JB, Ahr KF, Porosnicu Rodriguez KA, Shono Y, Slingerland AE, Docampo MD, Sung AD, Weber D, Alousi AM, Gyurkocza B, Ponce DM, Barker JN, Perales MA, Giralt SA, Taur Y, Pamer EG, Jenq RR, van den Brink MRM. Intestinal Microbiota and Relapse After Hematopoietic-Cell Transplantation. J Clin Oncol. 2017 May 20;35(15):1650-1659. doi: 10.1200/JCO.2016.70.3348. Epub 2017 Mar 15. — View Citation

Ravoet C, Feremans W, Husson B, Majois F, Kentos A, Lambermont M, Wallef G, Capel P, Beauduin M, Delannoy A. Clinical evidence for an engraftment syndrome associated with early and steep neutrophil recovery after autologous blood stem cell transplantation. Bone Marrow Transplant. 1996 Nov;18(5):943-7. — View Citation

Rodriguez-Lobato LG, Martinez-Roca A, Castano-Diez S, Palomino-Mosquera A, Gutierrez-Garcia G, Pedraza A, Suarez-Lledo M, Rovira M, Martinez C, Fernandez de Larrea C, Cibeira MT, Rosinol L, Lozano E, Marin P, Cid J, Lozano M, Moreno-Castano AB, Palomo M, Diaz-Ricart M, Gallego C, Hernando A, Segura S, Carreras E, Urbano-Ispizua A, Blade J, Fernandez-Aviles F. The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever. PLoS One. 2020 Nov 4;15(11):e0241778. doi: 10.1371/journal.pone.0241778. eCollection 2020. — View Citation

Samet A, Sledzinska A, Krawczyk B, Hellmann A, Nowicki S, Kur J, Nowicki B. Leukemia and risk of recurrent Escherichia coli bacteremia: genotyping implicates E. coli translocation from the colon to the bloodstream. Eur J Clin Microbiol Infect Dis. 2013 Nov;32(11):1393-400. doi: 10.1007/s10096-013-1886-9. Epub 2013 May 7. — View Citation

Satlin MJ, Chen L, Douglass C, Hovan M, Davidson E, Soave R, La Spina M, Gomez-Arteaga A, van Besien K, Mayer S, Phillips A, Hsu JM, Malherbe R, Small CB, Jenkins SG, Westblade LF, Kreiswirth BN, Walsh TJ. Colonization With Fluoroquinolone-Resistant Enterobacterales Decreases the Effectiveness of Fluoroquinolone Prophylaxis in Hematopoietic Cell Transplant Recipients. Clin Infect Dis. 2021 Oct 5;73(7):1257-1265. doi: 10.1093/cid/ciab404. — View Citation

Satlin MJ, Vardhana S, Soave R, Shore TB, Mark TM, Jacobs SE, Walsh TJ, Gergis U. Impact of Prophylactic Levofloxacin on Rates of Bloodstream Infection and Fever in Neutropenic Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2015 Oct;21(10):1808-14. doi: 10.1016/j.bbmt.2015.06.017. Epub 2015 Jul 3. — View Citation

Satlin MJ, Walsh TJ. Multidrug-resistant Enterobacteriaceae, Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus: Three major threats to hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2017 Dec;19(6):10.1111/tid.12762. doi: 10.1111/tid.12762. Epub 2017 Oct 25. — View Citation

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Sorrig R, Klausen TW, Salomo M, Vangsted A, Gimsing P. Risk factors for infections in newly diagnosed Multiple Myeloma patients: A Danish retrospective nationwide cohort study. Eur J Haematol. 2019 Feb;102(2):182-190. doi: 10.1111/ejh.13190. Epub 2018 Nov 28. — View Citation

Spitzer TR. Engraftment syndrome following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2001 May;27(9):893-8. doi: 10.1038/sj.bmt.1703015. — View Citation

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Van Lier YF, Van den Brink MRM, Hazenberg MD, Markey KA. The post-hematopoietic cell transplantation microbiome: relationships with transplant outcome and potential therapeutic targets. Haematologica. 2021 Aug 1;106(8):2042-2053. doi: 10.3324/haematol.2020.270835. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparison of effect of FRE colonization and fluoroquinolone prophylaxis on the microbiome between FRE carriers and FRE non-carriers	Comparison of effect of FRE colonization and fluoroquinolone prophylaxis on the microbiome between FRE carriers and FRE non-carriers	Duration between Apheresis Consultation and Day +100
Primary	Prevalence of FRE	Prevalence of FRE in patients undergoing autologous PBSC transplantation with dose-intense melphalan	Duration between Apheresis Consultation and Day +100
Secondary	Occurrence/Risk of Febrile Neutropenia (FN)	Occurrence of neutropenic fever during the first 28 days (4 weeks) after autologous PBSC transplantation in the treatment of multiple myeloma.	Within 28 days of the transplantation
Secondary	Occurrence/Risk of Blood Stream infection (BSI)	The occurrence of Gram-negative BSI among the FRE carriers and FRE non-carriers	Within 28 days of the transplantation
Secondary	Comparison of severity of GI toxicity between FRE carriers and FRE non-carriers	Comparison of severity of GI toxicity between FRE carriers and FRE non-carriers per the grade of GI toxicity	Duration between Apheresis Consultation and Day +100
Secondary	Comparison of Length of Stay (LOS) between FRE carriers and FRE non-carriers	Comparison of Length of Stay (LOS) between FRE carriers and FRE non-carriers by estimating time to discharge	Duration between Day of hospital admission and Day of hospital discharge (estimated duration between 11 - 15 days)
Secondary	Comparison of Engraftment Kinetics between FRE carriers and FRE non-carriers	Comparison of Engraftment Kinetics (absolute neutrophil count (ANC), absolute lymphocyte count (ALC), platelet) between FRE carriers and FRE non-carriers	Duration between Apheresis Consultation and Day +100

External Links

•   Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013
•   Prevention and Treatment of Cancer-Related Infections, Version: 2.2020