The aim of the trial is to improve efficacy of nivolumab in patients with relapsed or refractory HL previously treated with an anti-PD1 antibody. Primary objective of the trial is to show efficacy of the experimental treatment strategy.Secondary…
ID
Source
Brief title
Condition
- Lymphomas Hodgkin's disease
- Lymphomas Hodgkin's disease
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Abscopal response rate (ARR-6) with abscopal response centrally confirmed as
restaging result after RT to a single lesion and at least four but not more
than six nivolumab infusions (RE-6 result)
Secondary outcome
Overall abscopal response rate (OARR)
Overall response rate (ORR)
Duration of response (DOR)
Progression-free survival (PFS)
Overall survival (OS)
Adverse events (AE)
Feasibility aspects
Quality of life (QoL) and life situation (LS) aspects
Correlative studies
Background summary
Nivolumab is highly effective and well tolerated in relapsed / refractory HL,
nevertheless CR-rates are low and a considerable proportion of patients suffers
from progressive disease. Localized RT induces an immunogenic effect which
might work synergistically and facilitate augmented systemic (i.e. abscopal)
responses in combination with nivolumab.
Study objective
The aim of the trial is to improve efficacy of nivolumab in patients with
relapsed or refractory HL previously treated with an anti-PD1 antibody.
Primary objective of the trial is to show efficacy of the experimental
treatment strategy.
Secondary objectives are to further evaluate efficacy, show safety and
feasibility and perform correlative studies.
Study design
Single-arm two-stage phase II study
Intervention
Nivolumab 240 mg i.v. at 2-weekly intervals combined with 20Gy radiotherapy
(RT) to a preferably recently progressive and not pre-irradiated single lesion.
Nivolumab will be continued for a maximum of 18 months or until disease
progression or unacceptable toxicity.
Study burden and risks
All patients enrolled into the AERN trial will have previously received an
anti-PD1 antibody as the last preceeding line of therapy, either until PD or
for at least six months. Individual tolerability to the systemic checkpoint
blockade is hence already established outside the AERN trial. RT with 20 Gy to
a single HL lesion is a well established treatment for localized r/r cHL and
rarely associated with relevant toxicity.
Various previously described preclinical studies indicate synergistic systemic
effects of local RT and checkpoint inhibition and currently available case
report and a larger case series indicate feasibility, with no relevant
treatment-related morbidity or mortality reported, and remarkable efficacy of
such approaches.
Other treatment options in this setting are limited to palliative
individualized approaches, which are often conventional chemotherapies and
carry relevant toxicity, or best supportive care.
In summary, the benefit-risk ratio for the combination of localized RT and
continued anti-PD1 therapy in the setting of the AERN trial is considered
favorable.
Quality of Life is part of this trial and could be experienced as a burden.
Albertus Magnus Platz 1
Keulen 50923
DE
Albertus Magnus Platz 1
Keulen 50923
DE
Listed location countries
Age
Inclusion criteria
- Relapsed/refractory cHL with progression while treated with an anti-PD1
antibody or
Relapsed/refractory cHL with stable disease for > 6 months as best response to
ongoing anti-PD1 antibody therapy
- At least two distinct FDG-avid HL-lesions with at least 5 cm distance between
them, and one of them considered eligible for irradiation with 20Gy
- One but the irradiated lesion has to be outside the 10% isodose in RT
planning confirmed by the Central Response Evaluation Panel (CREP)
- Age 18 years and older, all sexes
Exclusion criteria
- Nodular lymphocyte-predominant HL or grey-zone lymphoma
- Evidence of active, non-infectious lung disorder with DLCOc < 50%
- History of long-term or ongoing ingestion of immunosuppressive agents >10mg
prednisone/d
- Any other serious disease or organ dysfunction which might impair protocol
treatment
Note: Patients on antiretroviral therapy (ART) with controlled HIV infection
(defined as sufficient ART compliance, non-measurable HIV and CD4+ T helper
cells > 200/µL) may be enrolled, if considered eligible for study treatment by
the investigator.
- Prior allogeneic stem-cell transplantation (alloSCT), if one or more of the
following conditions are met:
a. AlloSCT conducted <12 months prior to registration for the screening phase
b. Requiring continued immunosuppression beyond 7d) at registration for the
screening phase
c. History of acute graft-versus-host disease >= grade3
d. History of chronic graft-versus-host disease >= grade3
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2017-003334-82-NL |
| ClinicalTrials.gov | NCT03480334 |
| CCMO | NL71853.029.20 |