Pneumonia in the ImmunoCompromised - Use of the Karius Test for the Detection of Undiagnosed Pathogens

NCT04047719 | Completed DMC

• 1 other identifier: KDC-010
• Study Type: observational
• Target: 257
• Locations: 1 country
• Sites: 10

Brief Summary

Given the need for a more sensitive pathogen detection test in patients with immunocompromised pneumonia, this study will evaluate the performance of the Karius Test, a novel NGS blood test for the diagnosis of infectious diseases. We will compare the performance of the Karius Test to the results of microbiologic tests obtained as part of usual care for immunocompromised patients undergoing evaluation for suspected pneumonia.

Conditions

Pneumonia, Bacterial; Pneumonia, Viral; Pneumonia Fungal; Pneumonia Cavitary; Immunocompromised Host

Keywords

Pneumonia; NGS; cell free DNA; microbial cell free DNA; immunocompromised

Outcome Measures

Primary Outcomes (1)

• Additive clinical diagnostic value

  Percent of patients with ≥1 pathogen identified by the Karius Test collected at enrollment that is adjudicated as a probable cause of the subject's index pneumonia event with no pathogen identified as a probable cause of the subject's index pneumonia event from an adjudicated composite of all microbiologic test results performed per Standard of Care with results available within 7 days of study enrollment.

  7 days

Study Arms (1)

Intent-to-Diagnose Population

All subjects enrolled in the study that have at least one Karius Test with a valid result

Diagnostic Test: Karius Test

Interventions

Karius Test DIAGNOSTIC_TEST

Karius Test for detection of microbial cell free DNA (mcfDNA) in plasma

Intent-to-Diagnose Population

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Immunocompromised adult patients being evaluated for pneumonia who have undergone hematopoietic stem cell transplantation for any clinical indication or are receiving active chemotherapy for treatment of a hematologic malignancy.

You may qualify if:

• Subjects must meet all of the criteria in Section A and all of the criteria in either Section B, Section C or Section D.
• Section A:
• Patient is ≥ 18 years of age.
• Is currently admitted to the hospital.
• Has a suspected infectious pneumonia warranting diagnostic evaluation and treatment.
• Has undergone a diagnostic bronchoscopy for the evaluation of microbiologic etiology of pneumonia within 1 day prior to or has a scheduled bronchoscopy within 5 days following enrollment.
• Patient or patient's Legally Authorized Representative (LAR) has provided consent for the study.
• Section B:
• Has one of the following hematologic malignancies: Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), Lymphoma (any type), Multiple Myeloma (MM) or malignant transformation of Chronic Lymphocytic Leukemia (CLL/SLL).
• Are immunocompromised defined as having at least one of the following:
• Received chemotherapy within the last 45 days.
• A relapse of hematologic malignancy for which chemotherapy treatment is anticipated within the next 45 days.
• ANC\<500 for a minimum of 14 days and within 8 weeks prior to enrollment.
• Section C:
• Has undergone autologous hematopoietic stem cell transplantation (e.g. bone marrow transplantation) for one of the following hematologic malignancies: Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), Lymphoma (any type), or Multiple Myeloma (MM);), or malignant transformation of Chronic Lymphocytic Leukemia (CLL/SLL).

You may not qualify if:

• Patient is moribund and, in the opinion of the treating physician, is not expected to survive \>24 hours beyond the time of potential study enrollment visit.
• Microbiologic etiology of index pneumonia event has already been identified per local Standard of Care testing.
• Patient was previously enrolled in this study.
• Patient has any condition that, in the opinion of the treating physician, will prevent the patient from completing the study. (Note: a qualified patient may still enroll in the study if they decline to have exploratory research sample collected.)
• Patient is positive for SARS-COV-2 by any molecular testing within the 14 days prior to enrollment.

Sponsors & Collaborators

• Karius, Inc.: lead
• Duke Clinical Research Institute: collaborator

Study Sites (10)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UCSF Department of Medicine

San Francisco, California, 94143, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Tulane Section of Infectious Disease

New Orleans, Louisiana, 70112, United States

Location

Weill Cornell Medicine

New York, New York, 10021, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15025, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

Related Publications (9)

• Norton ME, Baer RJ, Wapner RJ, Kuppermann M, Jelliffe-Pawlowski LL, Currier RJ. Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities. Am J Obstet Gynecol. 2016 Jun;214(6):727.e1-6. doi: 10.1016/j.ajog.2015.12.018. Epub 2015 Dec 18.

  PMID: 26709085 BACKGROUND

• Alix-Panabieres C, Pantel K. Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy. Cancer Discov. 2016 May;6(5):479-91. doi: 10.1158/2159-8290.CD-15-1483. Epub 2016 Mar 11.

  PMID: 26969689 BACKGROUND

• Evans SE, Ost DE. Pneumonia in the neutropenic cancer patient. Curr Opin Pulm Med. 2015 May;21(3):260-71. doi: 10.1097/MCP.0000000000000156.

  PMID: 25784246 BACKGROUND

• Schuster MG, Cleveland AA, Dubberke ER, Kauffman CA, Avery RK, Husain S, Paterson DL, Silveira FP, Chiller TM, Benedict K, Murphy K, Pappas PG. Infections in Hematopoietic Cell Transplant Recipients: Results From the Organ Transplant Infection Project, a Multicenter, Prospective, Cohort Study. Open Forum Infect Dis. 2017 Mar 22;4(2):ofx050. doi: 10.1093/ofid/ofx050. eCollection 2017 Spring.

  PMID: 28491889 BACKGROUND

• Chen CS, Boeckh M, Seidel K, Clark JG, Kansu E, Madtes DK, Wagner JL, Witherspoon RP, Anasetti C, Appelbaum FR, Bensinger WI, Deeg HJ, Martin PJ, Sanders JE, Storb R, Storek J, Wade J, Siadak M, Flowers ME, Sullivan KM. Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2003 Sep;32(5):515-22. doi: 10.1038/sj.bmt.1704162.

  PMID: 12942099 BACKGROUND

• Harris B, Geyer AI. Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation. Clin Chest Med. 2017 Jun;38(2):317-331. doi: 10.1016/j.ccm.2016.12.008.

  PMID: 28477642 BACKGROUND

• Hohenthal U, Itala M, Salonen J, Sipila J, Rantakokko-Jalava K, Meurman O, Nikoskelainen J, Vainionpaa R, Kotilainen P. Bronchoalveolar lavage in immunocompromised patients with haematological malignancy--value of new microbiological methods. Eur J Haematol. 2005 Mar;74(3):203-11. doi: 10.1111/j.1600-0609.2004.00373.x.

  PMID: 15693789 BACKGROUND

• Blauwkamp TA, Thair S, Rosen MJ, Blair L, Lindner MS, Vilfan ID, Kawli T, Christians FC, Venkatasubrahmanyam S, Wall GD, Cheung A, Rogers ZN, Meshulam-Simon G, Huijse L, Balakrishnan S, Quinn JV, Hollemon D, Hong DK, Vaughn ML, Kertesz M, Bercovici S, Wilber JC, Yang S. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease. Nat Microbiol. 2019 Apr;4(4):663-674. doi: 10.1038/s41564-018-0349-6. Epub 2019 Feb 11.

  PMID: 30742071 BACKGROUND

• Bergin SP, Chemaly RF, Dadwal SS, Hill JA, Lee YJ, Haidar G, Luk A, Drelick A, Chin-Hong PV, Benamu E, Khawaja F, Nanayakkara D, Papanicolaou GA, Small CB, Fung M, Barron MA, Davis T, McClain MT, Maziarz EK, Madut DB, Bedoya AD, Gilstrap DL, Todd JL, Barkauskas CE, Bigelow R, Leimberger JD, Tsalik EL, Wolf O, Mughar M, Hollemon D, Duttagupta R, Lupu DS, Bercovici S, Perkins BA, Blauwkamp TA, Fowler VG Jr, Holland TL. Plasma Microbial Cell-Free DNA Sequencing in Immunocompromised Patients With Pneumonia: A Prospective Observational Study. Clin Infect Dis. 2024 Mar 20;78(3):775-784. doi: 10.1093/cid/ciad599.

  PMID: 37815489 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Pneumonia, Bacterial; Pneumonia, Viral; Pneumonia

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Virus Diseases

Study Officials

• Stephen Bergin, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2019
• First Posted: August 7, 2019
• Study Start: November 5, 2019
• Primary Completion: June 6, 2022
• Study Completion: June 6, 2022
• Last Updated: February 9, 2023

Record last verified: 2023-02

Locations

US (10)