A phase II study evaluating the effect of DA-EPOCH-R induction followed by nivolumab consolidation in patients with newly diagnosed high grade B cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements
- Conditions
- high grade B cell lymphoma (HGBL)10025320
- Registration Number
- NL-OMON52523
- Lead Sponsor
- HOVO
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 88
DA-EPOCH-R 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
outside 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.,
Inclusion criteria nivolumab: ,
* Complete metabolic response on end of induction 18F-FDG PET-CT assessed with
the Deauville response criteria (see 10.3) (or higher when due to inflammatory
response, only possible after written approval by the Principal Investigator).
* Patient has completed at least treatment of at least 5 induction cycles.
DA-EPOCH-R 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 < 30 mL/min (after
rehydration).
* Inadequate hepatic function: bilirubin > 3 times ULN (total) except patients
with Gilbert's syndrome as defined by > 80% unconjugated bilirubin.
* Inadequate hematological function: ANC < 1.0x109/L or platelets < 75x109 /L
before induction cycle 1 unless lymphoma related.
* CNS localization of the lymphoma. CSF analysis before start of treatment is
only necessary in case of suspicion of CNS localization.
* Female subject pregnant or breast-feeding.
* History of active malignancy during the past 5 years with the exception of
basal carcinoma of the skin or stage 0 cervical carcinoma.
* Active symptomatic ischemic heart disease, myocardial infarction, or
congestive heart failure within the past year. In case of cardiac history, an
echo or MUGA should be obtained and LVEF should exceed 40% to be eligible.
* Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled
diabetes, infection, hypertension, cancer, etc.) that would jeopardize the
patient's ability to receive the regimen with reasonable safety.
* HIV positivity.
* Active Hepatitis B or C infection as defined by positive serology and
transaminitis. Non-active Hepatitis B carriers may be included if protected
(see 9.2.3).
* Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix D).
* Subjects with active, known or suspected autoimmune disease. Subjects with
vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
condition only requiring hormone replacement, psoriasis not requiring systemic
treatment, or conditions not expected to recur in the absence of an external
trigger are permitted to enroll.
* Subjects with a condition requiring systemic treatment with either
corticosteroids (> 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., nivolumab exclusion criteria:, *
Inadequate renal function or creatinine clearance < 30 mL/min (after
rehydration). Creatinine clearance may be calculated by Cockcroft -Gault
formula:
CrCl = (140 - age [in years]) x weight [kg] (x 0.85 for females)
(0.815 x serum creatinine [µmol/L])
* Inadequate hepatic function: bilirubin > 3 times ULN (total) except patients
with Gilbert's syndrome as defined by > 80% unconjugated bilirubin.
* Subjects
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* 12 months DFS (defined as time from registration for consolidation to disease<br /><br>relapse or death, whichever comes first) of patients in CMR as assessed by end<br /><br>of DA-EPOCH-R treatment 18F-FDG PET-CT</p><br>
- Secondary Outcome Measures
Name Time Method