Clinical trial NCT04226937: DLBCL Interim Response Evaluation for Customised Therapy
Official title: DLBCL Interim Response Evaluation for Customised Therapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: High-grade B-cell Lymphoma
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Cancer Research UK Cambridge Institute
First posted: 2020-01-13
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with diffuse Large B Cell Lymphoma (DLBCL) or closely related high-grade B cell lymphomas including, but not limited to:

* DLBCL NOS
* Transformed follicular lymphoma
* High grade B cell lymphoma with rearrangement of BCL2/BCL6 and MYC
* Plasmablastic lymphoma
* Primary Mediastinal Large Cell lymphoma
* Burkitt lymphoma
* Primary Central Nervous System lymphoma
* High grade B cell lymphoma NOS

Undergoing Standard of Care treatment for their lymphoma.

Brief summary: The aim of the DIRECT Study is to establish a robust pipeline to identify those patients with high-grade B cell lymphoma most suitable for novel agent clinical trials based upon genomic subtype and an integrated response evaluation determined early in first-line therapy.

Detailed description: This will be done by integrating data and samples collected from patients undergoing standard of care treatment for high-grade B cell lymphoma

Data will be integrated from

1. Clinical risk factors from the International Prognostic Index (IPI)
2. Up-front genomic subtype based on molecular profiling of diagnostic biopsy
3. Serial ctDNA monitoring during treatment.
4. Radiological response imaging

Eligibility criteria: * Have given written informed consent to participate.
* Age ≥ 18 years at the time of consent.
* Histologically confirmed diagnosis of previously untreated high-grade B cell lymphoma.
* Planned to receive immunochemotherapy as first-line therapy, e.g. R-CHOP therapy.
* Planned or completed standard of care imaging (CT or PET-CT)
* Able to give blood.

Exclusion Criteria:

* Unable to receive immunochemotherapy as first-line therapy due to co-morbidity or personal choice.
* Patients who have already started high dose steroids as a treatment for their lymphoma.
* Known diagnosis of infectious blood-borne virus e.g. Hep B, Hep C or HIV.

Primary outcomes:
measure: Establish a robust molecular monitoring pipeline.
timeFrame: 3-5 years
measure: Successful identification of trackable mutations in collected samples. Feasibility will be met if more than 75% of the samples yield trackable mutations across the whole study.
timeFrame: 3-5 years
Secondary outcomes:
measure: Assess the utility of serial ctDNA assessment as a predicator of clinical outcome in high-grade B cell lymphoma.
timeFrame: 5 years
measure: Assess the utility of integrated data from clinical risk factors (IPI), up-front genotype, serial ctDNA response and radiological assessment (CT or PET-CT).
timeFrame: 3-5 years
measure: When the pipeline is optimised can these 4 parameters be available within 6 weeks, i.e. by completion of Cycle 2.
timeFrame: 3-5 years
Other outcomes:
measure: Identification of the de novo somatic variants in high-grade B cell lymphoma from collected ctDNA and tissue samples.
timeFrame: 3-5 years
measure: Assess the utility of ctDNA to track clonal evolution in patients undergoing treatment for high-grade B cell lymphoma.
timeFrame: 3-5 years
Locations:
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: Cambridgeshire
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: Daniel Hodson, PhD MRCP FRCPath
role: PRINCIPAL_INVESTIGATOR
References: