Assessing the Presence of CT-DNA in Lymphoma Associated HLH

NCT05702502 | Recruiting

• 1 other identifier: 22CH022
• Study Type: observational
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Haemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening blood disease which causes severe inflammation with symptoms similar to severe sepsis. It is hard to diagnose. The most common cause of HLH in adults is lymphoma (blood cancer). Outcomes for adults with HLH and cancer are serious, and most die after days or weeks because they have been diagnosed or treated too late. It is likely that many cases where patients died of HLH with no underlying cause actually had cancer. Recently it has been found that patients with certain types of lymphoma have DNA which comes directly from their cancer (circulating tumour DNA; ctDNA). Aggressive lymphomas release a lot of ctDNA which can be detected in the blood of patients. This study will look for ctDNA in patients with HLH, and see if it is possible to use it to diagnose lymphoma earlier. Patients will provide a small additional blood sample for analysis. Diagnosing lymphoma more rapidly would mean more people could get the correct treatment for the lymphoma which has caused their HLH. They could receive the correct treatment sooner. Earlier diagnosis and treatment could improve survival for these patients.

Conditions

Lymphoma; Haemophagocytic Lymphohistiocytosis

Outcome Measures

Primary Outcomes (1)

• Identification of lymphoma-specific mutations in ctDNA from patients with lymphoma driven HLH.

  For those patients found to have lymphoma driven haemophagocytic syndrome we will assess whether we can find the presence of cell free tumour DNA in blood.

  Up to 2 years

Secondary Outcomes (2)

• Assess the utility of integrated data from clinical risk factors (IPI), up-front genotype, and radiological assessment (CT or PET-CT) with ctDNA findings.

  Up to 2 years

• Assessing the feasibility of returning central laboratory data in a clinically useful timeframe.

  Up to 2 years

Eligibility Criteria

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

Study Population

Patients with HLH are usually unwell and hospitalised. Patients will be identified by the clinical (direct care) teams following a clinical diagnosis of HLH as part of routine clinical practice.

You may qualify if:

• Informed consent.
• Age ≥18 years.
• Clinically confirmed HLH.
• High dose steroids and/or systemic anti-cancer therapy (SACT) for \<72 hours for the current episode of HLH (anakinra is not considered SACT). Prior steroid use \>14 days at the time of consent is permitted.
• Patients with recurrent HLH may be included.
• Patients already known to have underlying lymphoma, or have relapsed lymphoma may be included.

You may not qualify if:

• Cause of HLH already known to be due to a non-malignant cause.

Sponsors & Collaborators

• Nottingham University Hospitals NHS Trust: lead

Study Sites (1)

Nottingham Univeristy Hospitals NHS Trust

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Circulating tumour DNA Tumour biopsy Peripheral blood white cells (for germline DNA)

MeSH Terms

Conditions

Lymphoma; Lymphohistiocytosis, Hemophagocytic

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: January 27, 2023
• Study Start: June 30, 2023
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: April 8, 2025

Record last verified: 2025-04

Locations

GB (1)