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

• Sponsor: Karius, Inc.
• Collaborator: Duke Clinical Research Institute
• Information provided by (Responsible Party): Karius, Inc.

Study Description

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.

Condition or disease	Intervention/treatment
Pneumonia, Bacterial; Pneumonia, Viral; Pneumonia Fungal; Pneumonia Cavitary; Immunocompromised Host	Diagnostic Test: Karius Test

Detailed Description:

Pneumonia is a major cause of morbidity and mortality in highly immunocompromised individuals such as patients with hematologic malignancies or undergoing hematopoietic stem-cell transplantation. These patients can be infected by a broad range of potential pathogens, including viral, bacterial, and fungal etiologies and sometimes with multiple pathogens simultaneously. Diagnostic testing often fails to identify a microbial etiology for lower respiratory illness even with bronchoalveolar lavage (BAL). In fact, culture methods, PCR, and antigen testing on BAL samples yields a positive result only 30-67% of the time. Additionally, Idiopathic Pulmonary Syndrome (IPS), a non-infectious pulmonary complication of transplant, can have many overlapping symptoms with infectious pneumonia. Treatment for IPS is administration of steroids which can exacerbate infections. Given these reasons, there is a need for better diagnostics to aid in the management of immunocompromised patients with pneumonia.

Karius has developed a microbial cell-free plasma next-generation sequencing test for pathogen detection capable of detecting >1,000 organisms including DNA viruses, bacteria, yeasts, molds, and other eukaryotic pathogens. The test is performed in a CLIA-certified/CAP-accredited laboratory with results typically provided within one day from sample receipt. Given the need for a more sensitive diagnostic test for pneumonia in this population, we are evaluating the performance of the Karius Test for pathogen detection.

Study Design

• Study Type: Observational
• Estimated Enrollment: 195 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Pneumonia in the ImmunoCompromised - Use of the Karius Test for the Detection of Undiagnosed Pathogens
• Estimated Study Start Date: August 31, 2019
• Estimated Primary Completion Date: August 31, 2020
• Estimated Study Completion Date: December 31, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
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; Karius Test for detection of microbial cell free DNA (mcfDNA) in plasma

Outcome Measures

Primary Outcome Measures :

1. Additive clinical diagnostic value [ Time Frame: 7 days ]
   Percent of patients with ≥1 pathogen identified by the Karius Test at enrollment adjudicated as a definite or probable cause of the subject's index pneumonia event with no pathogen identified as a definite or probable cause of the subject's index pneumonia event from an adjudicated composite of all microbiologic test results performed per standard of care iwth results available within 7 days of study enrollment

Biospecimen Retention:   Samples With DNA

Blood

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Immunocompromised patients with hematologic malignancies ≥ 18 years of age who are being evaluated for infectious pneumonia

Criteria

Inclusion Criteria:

Patients are eligible for the study if they meet all of the following criteria:

1. ≥ 18 years of age
2. Have one of the following hematologic malignancies: Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), Lymphoma (all types), or Multiple Myeloma (MM)

3. Are immunocompromised defined as having at least one of the following:

   1. Received chemotherapy within the past 30 days
   2. Undergone hematopoietic stem cell transplantation (HSCT) within the past 1 year
   3. Active graft vs host disease (GVHD) requiring immunosuppressive pharmacologic treatment
4. Are admitted to the hospital with suspected infectious pneumonia warranting diagnostic evaluation and treatment
5. Have a planned diagnostic bronchoscopy or have undergone a diagnostic bronchoscopy for the evaluation of the microbiologic etiology of pneumonia within the 24 hours prior to enrollment

Exclusion Criteria:

Patients are not eligible for the study if they meet any of the following criteria:

1. Patient or patient's legally authorized representative does not provide consent for the study
2. 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
3. Microbiologic etiology of index pneumonia event has already been identified per usual care testing
4. Patient was previously enrolled in this study
5. Patient has any condition that, in the opinion of the treating physician, will prevent the patient from completing the study

Contacts and Locations

Contacts

Contact: Sudeb Dalai, MD, PhD; 650-409-5007 ext 167; sudeb.dalai@kariusdx.com

Contact: Stacy Melusky, BS; 510-258-9079; stacy.meluskey@kariusdx.com

Sponsors and Collaborators

Karius, Inc.

Duke Clinical Research Institute

Investigators

• Principal Investigator: Stephen Bergin, MD; Duke University

More Information

Publications:

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.

Alix-Panabières 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. Review.

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. Review.

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.

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.

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. Review.

Hohenthal U, Itälä M, Salonen J, Sipilä J, Rantakokko-Jalava K, Meurman O, Nikoskelainen J, Vainionpää 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.

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.

• Responsible Party: Karius, Inc.
• ClinicalTrials.gov Identifier: NCT04047719 History of Changes
• Other Study ID Numbers: KDC-010
• First Posted: August 7, 2019
• Last Update Posted: August 12, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Karius, Inc.:

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

Additional relevant MeSH terms:

Pneumonia; Pneumonia, Bacterial; Pneumonia, Viral; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Bacterial Infections; Virus Diseases