Diffuse large B cell lymphoma MedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Product Name: cyclophosphamide
Product Code: DA-EPOCH-R
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Other descriptive
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? High-grade B-cell lymphoma, with MYC in combination with BCL2 and/or BCL6 rearrangements as assessed by FISH according to the WHO 2016 classification including high-grade B-cell lymphoma with MYC and BCL2 rearrangements, transformed from previously untreated FL. ? Age = 18 year ? Patient started with or has received one course of full dose R-CHOP or DA-EPOCH-R (cycle 1). Starting with DA-EPOCH-R in cycle 1 is only allowed when FISH results (confirming DH/TH diagnosis) are directly available at diagnosis. [Reversed R-CHOP (cyclophosphamide, vincristine and doxorubicin on day 5) is allowed; local radiation or short course (max 7 days) of steroids (max 100 mg/day) before R-CHOP is allowed. Mini-R-CHOP is not allowed]. ? WHO performance status 0-3 during or after induction cycle 1 (see appendix C). ? Ann Arbor stage II-IV at diagnosis (see appendix A). ? 18F-FDG PET scan and contrast enhanced CT-scan performed preferably within 28 days before start first induction cycle. When the PET or CT-scan is performed outsite the 28-day window, consultation and written approval by the Principal Investigator for potential patient inclusion are necessary. ? Measurable disease: on contrast enhanced CT-scan at least 1 lesion/node with a long axis of >1.5 cm and at least one 18F-FDG avid lesion. ? Negative pregnancy test at study entry. ? Patient is willing and able to use adequate contraception until 6 months post last treatment administration. ? Written informed consent. ? Patient is capable of giving informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 51 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 51
Exclusion criteria
Exclusion criteria: ? All histopathological diagnoses other than DH/TH-HGBL (like testicular large B-cell lymphoma or primary mediastinal B-cell lymphoma) according to WHO 2016 classification. ? Known history of indolent lymphoma previously treated with immunochemotherapy. ? Inadequate renal function or creatinine clearance 3 times ULN (total) except patients with Gilbert's syndrome as defined by > 80% unconjugated bilirubin. ? Inadequate hematological function: ANC 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. ? Prior treatment with an anti-PD1, anti-PDL1, anti-PDL2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways. ? Severe neurological or psychiatric disease. ? Current participation in another clinical trial interfering with this trial. ? Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule. ? Claustrophobia precluding PET-CT.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To increase 12 months DFS of DH/TH-HGBL patients in CMR after DA-EPOCH-R from 70% to 85% with nivolumab consolidation treatment;Secondary Objective: ? To evaluate CMR rate after completion of DA-EPOCH-R ? To evaluate 18 months PFS and OS of all patients ? To evaluate 12 months overall survival under consolidation (OSc) of patients registered for consolidation ? To evaluate safety of nivolumab treatment ? To explore the accuracy of mid-treatment 18F-FDG PET-CT to predict CMR end-of-treatment. ? To explore the efficacy of nivolumab with regard to induction of MRD negativity by circulating tumor DNA and extracellular vesicle associated microRNA ? To explore PD1/PDL1 expression in relation to NGS, GEP and to outcome ? To explore T cell subsets and clonality during treatment and in relation to MRD;Primary end point(s): ? 12 months DFS (defined as time from registration for consolidation to disease relapse or death, whichever comes first) of patients in CMR as assessed by end of DA-EPOCH-R treatment 18F-FDG PET-CT.;Timepoint(s) of evaluation of this end point: The endpoints will be evaluated when relevant data for all patients are available | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? CMR rate on 18F-FDG PET-CT after DA-EPOCH-R ? 18 months PFS (defined as time from registration to disease progression, relapse or death, whichever comes first) , ? 18 months OS (defined as time from registration until death from any cause; patients still alive or lost to follow up are censored at the date they were last known to be alive) of all patients ? 12 months overall survival under consolidation (OSc), defined as time from registration for consolidation until death from any cause. Patients still alive or lost to follow up are censored at the date they were last known to be alive ? Rate of CTCAE grade >=2 toxicities ? Rate of conversion to MRD negativity during consolidation ? Assessment of the predictive value of mid-treatment 18F-FDG PET-CT with respect to CMR at the end of DA-EPOCH-R therapy ? Association of PD1/PDL1 expression in relation NGS, GEP and to outcome ? Association of MRD measurements by circulating tumor DNA and microRNA ? Association of T cell subsets and clonality during nivolumab treatment and to MRD;Timepoint(s) of evaluation of this end point: The endpoints will be evaluated when relevant data for all patients are available | — |
Countries
Belgium, Netherlands
Contacts
Public ContactHOVON Data Center
Erasmus MC, HOVON Data Center
Outcome results
None listed