DLBCL Interim Response Evaluation for Customised Therapy

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

Official Title
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DLBCL Interim Response Evaluation for Customised Therapy

Conditions
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High-grade B-cell Lymphoma

Intervention / Treatment
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* Other: Not Applicable as this is a translational, sample collection study.


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Not Applicable as this is a translational, sample collection study.|Patients will take their normal standard of care treatment for their lymphoma, as per agreed with the patient's doctor. Blood samples will be collected at Baseline, during the first 3 cycles of Treatment, at End of Treatment, at 6- and 12-months after End of Treatment and at relapse/progression if applicable. Surplus Tissue biopsy will be collected at Baseline and at relapse/progression if applicable. In rare cases research-specific tissue biopsy may be collected if appropriate.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish a robust molecular monitoring pipeline. |  | 3-5 years | 
| 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. |  | 3-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the utility of serial ctDNA assessment as a predicator of clinical outcome in high-grade B cell lymphoma. |  | 5 years | 
| Assess the utility of integrated data from clinical risk factors (IPI), up-front genotype, serial ctDNA response and radiological assessment (CT or PET-CT). |  | 3-5 years | 
| When the pipeline is optimised can these 4 parameters be available within 6 weeks, i.e. by completion of Cycle 2. | Clinical risk factors from the International Prognostic Index (IPI) Up-front genomic subtype based on molecular profiling of diagnostic biopsy Serial ctDNA monitoring during treatment. Radiological response imaging | 3-5 years |