DLBCL Interim Response Evaluation for Customised Therapy (DIRECT)

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.

Study Overview

• Status: Recruiting
• Conditions: High-grade B-cell Lymphoma
• Intervention / Treatment: Other: Not Applicable as this is a translational, sample collection study.

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

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Silvia Tarantino; Phone Number: +44(0)122325634; Email: silvia.tarantino@addenbrookes.nhs.uk

Study Locations

• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Recruiting
      • Cambridge University Hospitals NHS Foundation Trust
      • Contact: Phil Barry, PhD; Email: philip.barry@addenbrookes.nhs.uk
      • Principal Investigator: Daniel Hodson, PhD MRCP FRCPath

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

• 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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Identification of the de novo somatic variants in high-grade B cell lymphoma from collected ctDNA and tissue samples.	3-5 years
Assess the utility of ctDNA to track clonal evolution in patients undergoing treatment for high-grade B cell lymphoma.	3-5 years

Collaborators and Investigators

• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Collaborators: AstraZeneca; Cancer Research UK Cambridge Institute
• Investigators: Principal Investigator: Daniel Hodson, PhD MRCP FRCPath, Cambridge University Hospitals NHS Foundation Trust

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 17, 2020
• Primary Completion (ANTICIPATED): September 1, 2025
• Study Completion (ANTICIPATED): September 1, 2025

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 10, 2020
• First Posted (ACTUAL): January 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): August 5, 2022
• Last Update Submitted That Met QC Criteria: August 4, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: DIRECT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No