DLBCL Interim Response Evaluation for Customised Therapy

High-grade B-cell Lymphoma Clinical Trial

— DIRECT  

Official title:

DLBCL Interim Response Evaluation for Customised Therapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04226937
• Other study ID #: DIRECT
• Status: Recruiting
• Start date: September 17, 2020
• Est. completion date: September 1, 2025

Study information

• Verified date: August 2022
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: Silvia Tarantino
• Phone: +44(0)122325634
• Email: silvia.tarantino[@]addenbrookes.nhs.uk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 1, 2025
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• High-grade B-cell Lymphoma

Intervention

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.

Locations

Country	Name	City	State
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge	Cambridgeshire

Sponsors (3)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust	AstraZeneca, Cancer Research UK Cambridge Institute

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Identification of the de novo somatic variants in high-grade B cell lymphoma from collected ctDNA and tissue samples.		3-5 years
Other	Assess the utility of ctDNA to track clonal evolution in patients undergoing treatment for high-grade B cell lymphoma.		3-5 years
Primary	Establish a robust molecular monitoring pipeline.		3-5 years
Primary	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	Assess the utility of serial ctDNA assessment as a predicator of clinical outcome in high-grade B cell lymphoma.		5 years
Secondary	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
Secondary	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