Clinical trial NCT04237168: Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL)
Official title: Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL): Prognostic Implications and Assessment of Tumor Response
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lymphoma, Large B-Cell, Diffuse
Keywords: Diffuse large B cell lymphoma
immunoglobulin gene next generation sequencing
liquid biopsy
Lead sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor class: OTHER
First posted: 2020-01-23
Enrollment: 30
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: newly DLBCL patients (diagnosed and treated in "Hospital de la Santa Creu i Sant Pau")

Brief summary: This study will evaluate IgNGS at different time points in newly diagnosed DLBCL patients homogeneously treated (RCHOP) to address its correlation with conventional techniques (i.e., positron emission tomography/computed tomography imaging (PET/CT) and outcome.

Detailed description: In B-cell malignancies, every lymphocyte clone expresses a unique antigen receptor structure, therefore immunoglobulin gene rearrangements (the sequence of nucleotides at the V(D)J recombination site) serves as a specific marker for each clone. Methods of analysis have changed over time to improve the sensitivity and to allow its application in clinical settings.

Diffuse Large B-cell lymphoma (DLBCL) displays molecular heterogeneity. In this context, IgNGS allows for detection of tumor clonotype from plasma (ctDNA) (Liquid Biopsy-LB) of DLBCL patients with high sensitivity and specificity. ctDNA can be tracked with this methodology in the vast majority (\>90%) of patients, in contrast to NGS-methods based on genotyping for specific DLBCL mutations, which have overall low frequency. Furthermore, most newly discovered neoantigens in lymphoma derive from immunoglobulin variable sequences, supporting the relevance of the analysis of this particular region in contrast to the use of specific B-cell mutations. Importantly, preliminary studies on clonotype detection by IgNGS at the end of treatment correlate with outcome (poorer progression-free survival) and the persistence or reemergence of the tumor clonotype by ctDNA studies may anticipate the clinical relapse. We propose to evaluate IgNGS at different time points in newly diagnosed DLBCL patients treated with RCHOP to address its correlation with conventional techniques (i.e., PET/CT imaging) and outcome.

Eligibility criteria: Inclusion Criteria: patients diagnosed with de novo DLBCL, all ages, treated with R-CHOP. Patients with DLBCL not otherwise specified (NOS) according to World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO) 2016 would be included. In addition, those with "high-grade B cell lymphoma (including both NOS and those with Myc and bcl2 and/or bcl6 alterations) will be also included.

Exclusion Criteria:

* Primary mediastinal DLBCL.
* Transformed DLBCL
* Patients HIV+
* Central Nervous System (CNS) DLBCL
* All other DLBCL not included under "NOS" classification, according to WHO 2016 (except those specifically indicated in "inclusion criteria").

Primary outcomes:
measure: Association between ctDNA level and clinical response at the end of treatment
timeFrame: 12-18 months
Secondary outcomes:
measure: Correlation between detection of tumor clonotype ctDNA and relapse
timeFrame: 18 months
measure: Impact of IgNGS at the end of treatment and 6 months after treatment on outcome (as measured by progression-free survival PFS)
timeFrame: 18 months
Other outcomes:
measure: Clinical impact of the described technique for minimal residual disease (MRD) detection in patients with DLBCL
timeFrame: 3 years
measure: Feasibility of the described technique
timeFrame: 3 years
Locations:
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
Study officials:
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: Javier Briones
role: PRINCIPAL_INVESTIGATOR
References:
citation: Herrera AF, Armand P. Minimal Residual Disease Assessment in Lymphoma: Methods and Applications. J Clin Oncol. 2017 Dec 1;35(34):3877-3887. doi: 10.1200/JCO.2017.74.5281. Epub 2017 Sep 21.
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citation: Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, Shovlin M, Jaffe ES, Staudt LM, Lai C, Steinberg SM, Chen CC, Zheng J, Willis TD, Faham M, Wilson WH. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015 May;16(5):541-9. doi: 10.1016/S1470-2045(15)70106-3. Epub 2015 Apr 1.