1 - To determine the feasibility of MRD detection using next generation sequencing (NGS) on circulating tumor DNA (ctDNA) from PTLD patients using a gene panel previously used in diffuse large B-cell lymphoma (DLBCL) 2 - To explore the mutational…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's B-cell
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1 - Detection of ctDNA at diagnosis and response evaluation
Secondary outcome
2 - Sensitivity and specificity of plasma ctDNA genotyping in comparison with
tumor sample DNA (gDNA) as gold standard
3 - Changes in ctDNA abundance throughout therapy
4 - Clinical end-points: progression free survival (PFS), overall survival
(OS), event free survival (EFS), disease specific survival (DSS)
Background summary
Post-transplant lymphoproliferative disorder (PTLD) is a serious complication
after solid organ (SOT) and hematopoietic stem cell transplantation (HSCT),
associated with significant morbidity and mortality. Initial treatment consists
of tapering immune suppression and rituximab monotherapy. 18F-flurodeoxyglucose
positron emission tomography/computed tomography (18F-FDG-PET/CT) has become
the main tool to assess remission status, drive decisions on treatment
alteration and identify relapse in patients with PTLD. In case of positive
18F-FDG-PET/CT following rituximab, treatment is escalated with R-CHOP. However
18F-FDG-PET/CT false positives results are commonly reported and it has limited
prognostic value (positive predictive value of 38% negative predictive value of
92%). Minimal residual disease (MRD) from circulating tumor DNA (ctDNA)
fragments occurs under the detection threshold of 18F-FDG-PET/CT. With a blood
sample one may be able to monitor MRD, thought to be responsible for disease
progression and relapse. MRD may become an early response indicator used to
guide treatment. We will investigate the feasibility of MRD monitoring in
PTLD patients and perform an exploratory study to evaluate if MRD monitoring
may be used to trace disease status during treatment and identify early
responders from (non-) responders.
Study objective
1 - To determine the feasibility of MRD detection using next generation
sequencing (NGS) on circulating tumor DNA (ctDNA) from PTLD patients using a
gene panel previously used in diffuse large B-cell lymphoma (DLBCL)
2 - To explore the mutational landscape of PTLD by whole exome sequencing and
validate the study*s gene panel
3 - To investigate the dynamics of ctDNA at diagnosis, interim and at
end-of-treatment in relation to rituximab and R-CHOP treatment
4 - To compare ctDNA abundance with 18F-FDG-PET/CT results in patients
responding to therapy vs refractory or relapsing patients.
Study design
An exploratory prospective multicenter, multinational cohort study.
Tissue biopsies are performed at diagnosis as part of routine diagnostics.
18F-FDG-PET/CT scans and blood sampling for EBV measurements at diagnosis,
after 4 or 8 courses with rituximab and after R-CHOP therapy are performed as
standard of care. MRD measurements will be performed on blood samples obtained
at diagnosis and after the 4 cycle of rituximab. In case of responsive disease
MRD will be determined after the 8th cycle of rituximab. In case of
unresponsive disease, MRD will be determined after cycle 2 and 4 of R-CHOP
Study burden and risks
No serious adverse events are expected from a routine venipuncture performed by
specialized personnel.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
- Patients having undergone a solid organ transplantation or hematopoietic stem
cell transplantation.
- Histologically proven CD20+ monomorphic PTLD (with or without EBV association)
- Age > 18 years
- Intent to treat patient according to standard protocol (rituximab / R-CHOP).
Clinicians are allowed to adapt protocol in the best interest of the patient
- Measurable disease on 18F-FDG-PET/CT at diagnosis
-Patient*s written informed consent and written consent for data collection.
Exclusion criteria
-A complete surgical resection of tumor.
-Upfront treatment with external beam radiation therapy.
-Known to be HIV positive.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66412.042.18 |
| Other | NTR: Waiting number |