A Phase 2 interventional study of R-CHOEP and DA-EPOCH-R in Lymphoma, Large B-Cell, Diffuse, sponsored by Nordic Lymphoma Group. Active, not recruiting at 16 sites in 4 countries. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2024-06-21.
Sponsored by Nordic Lymphoma Group · Phase 2, Interventional, and Treatment
This study is testing whether stratification of the patients according to biological risk factors for different treatment groups will improve the outcome of patients with clinically high diffuse large B-cell lymphoma (DLBCL).
For young clinically high-risk diffuse large B-cell lymphoma (DLBCL) patients the optimal therapy has not been established. Previous Nordic phase II studies, where dose-dense chemoimmunotherapy (R-CHOEP-14) with systemic CNS prophylaxis (HD-Mtx and HD-AraC) was given, demonstrated favorable outcome in comparison to historical controls. However, the patients with biological risk factors, such as translocation of bcl2 and myc oncogenes or and/or high BCL2 and MYC expression or deletion 17p and/or high P53 expression had significantly higher risk of death, as compared to patients without aberrations. The figures provide evidence for an unmet clinical need for the patients with biological risk factors, and underscore the importance of a clinical trial, where both biological and clinical risk factors play a role in the treatment planning.
In this trial treatment intensity varies according to presence or absence of biological risk factors. All patients receive a prephase medication consisting of prednisone and vincristine and two cycles of R-CHOP and high dose (HD) methotrexate. Subsequently, depending on the biological risk factors either four additional cycles of R-CHOEP (standard arm with no risk factors) or four dose adjusted R-EPOCH courses (experimental arm with risk factors) are given, followed by one course of high dose cytarabine (Ara-C) and R. R-CHOEP courses should be given with a two-week and R-EPOCH with a three-week interval.
Histologically confirmed CD20+ DLBCL based on revised WHO 2008 Lymphoma Classification. The following subgroups and variants can be included:
Patients in at least stage II with age adjusted IPI score of 2 or 3:
And/or patients with site specific risk factors for CNS recurrence defined as follows
Exclusion Criteria:
Biologically low risk group, R-CHOEP-14
Combination Product: R-CHOEP
Biologically high risk group, DA-EPOCH-R
Combination Product: DA-EPOCH-R
rituximab, cyclophosphamide, doxorubicin, etoposide, vincristine, prednisone
dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab
Time to treatment failure (TTF) of the patients with biological risk factors
Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.
Time frame: At 3 years
Time to treatment failure (TTF) at 3 years from date of registration of all patients and the patients in the low risk group
Interval between the registration date and the date of documented progression or lack of response, first relapse, death for any reason or discontinuation/change of therapy because of toxicity, whichever occurs first. Otherwise, patients will be censored at the last date they were known to be alive. For patients not responding at any time point on study treatment, TTF is defined as one day.
Time frame: At 3 years
Incidence of treatment-emergent adverse events (Safety and tolerability)
Number of patients with treatment-related adverse events graded according to the NCI CTCAE v 4.03
Time frame: During the treatment period at the end of each cycle (14 or 21 days) up to 6 months. In addition, severe late toxicities during follow-up at 6 months intervals through study completion, an average of 5.5 years.
Clinical response rate of all patients and the patients with biological risk factors
Number of patients with complete or partial response
Time frame: At the end of treatment cycles 2 and 7. Each cycle is two (group A) or three weeks (group B)
CNS relapse rate
Number of patients with CNS progression
Time frame: At 1,5 years
Progression free survival rate (PFS) of all patients and the patients with biological risk factors
Time frame: At 3 years
Overall survival rate (OS) of all patients and the patients with biological risk factors
Time frame: At 3 years
Molecular correlates for survival
Identification of genomic aberrations (for example mutations and translocations), gene expression profiles and protein expression from the tumor tissue and circulation that predict clinical course of the disease
Time frame: At 3 years
Plan to share: Yes — individual deidentified participant data (including data dictionaries) will be shared
Supporting information: Study protocol, Sap, Icf, Csr
This study is active, not recruiting, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.
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Nordic Lymphoma Group