This study has been transitioned to CTIS with ID 2023-508478-27-00 check the CTIS register for the current data. The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET results in improved efficacy…
ID
Source
Brief title
Condition
- Lymphomas Hodgkin's disease
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Modified progression-free survival rate at 2 years after start of treatment
(2yr-mPFS).
The following are considered events for the primary endpoint:
# progression/relapse;
# start of new treatment for cHL when not in CR after completing protocol
treatment (including radiotherapy)
# death from any cause.
Secondary outcome
- Patients with negative FDG-PET after 1 cycle of BrAVD (central assessment)
- Response rate according to Lugano Criteria at end of protocol treatment i.e.
after chemotherapy and after radiotherapy (if administered),
- Progression-free survival (where progression, relapse and death from any
cause are considered events).
- Overall survival
- Safety and tolerability
Exploratory:
- Response rate according to RECIL 2017
- To assess the degree of association between serum TARC level and FDG-PET
result both after one cycle of BrAVD among patients with pre-treatment TARC
elevation (see translational research in chapter 10)
- To identify markers that are potentially predictive for response or toxicity
or markers that can be used for treatment response monitoring (see
translational research chapter 10)
Background summary
Standard treatment for advanced Hodgkin lymphoma (HL) consists of chemotherapy:
ABVD or escBEACOPP, followed by radiotherapy on FDG-PET positive residual
disease after chemotherapy.
Although long-term progression free survival after escBEACOPP treatment (PFS
85-90%) is superior to ABVD (PFS 65-70%), escBEACOPP has more significant
short-and long-term adverse effects than ABVD, and a potential difference in
overall survival between patients treated with ABVD or escBEACOPP is debatable.
Moreover comparable data is derived from studies in which individual treatment
was not yet guided by the results of metabolic response during treatment by
interim FDG-PET.
Currently, interim PET guidend treatment is standard of care for advanced HL.
Adjustment of treatment, i.e. escalation of deëscalatie of treatment intensity
is based on (metabolic) tumor response assessed by interim FDG-PET after 2
cycles of chemotherapy. FDG-PET after 1 cycle of chemotherapie (PET1) has
recently been shown to have an even better negative predictive value. (NPV
PET1: 98%, PET2: 90%)
Brentuximab-vedotin, an anti-CD30 Monoclonal antibody-toxine conjugate
(vedotin) has high effectivity in HL. This drug is currently registered as 2nd
or 3rd line treatment for HL. In up-front treatment for advanced HL,
Brentuximab vetotin combined with AVD (without Bleomycine, i.e. BrAVD), was
more effective than ABVD (phase III study); Brentuximab-vedotin incorporated in
a escBEACOPP derived- ECADD combination (BrECADD) has been shown to be less
toxic than escBEACOPP, and equally effective (phase II study).
Study objective
This study has been transitioned to CTIS with ID 2023-508478-27-00 check the CTIS register for the current data.
The main objective of this trial is to assess whether treatment adaptation
based on a very early FDG-PET results in improved efficacy while minimizing
treatment toxicity in advanced stage HL patients treated with BV-containing
regimens, BrAVD and BrECADD.
This will be primarily assessed by modified progression-free survival.
The secondary objectives are:
- To asses number of negative FDG-PET scans (Deauville score 1-3) after 1 cycle
of BrAVD
- To assess response according to Lugano Criteria at end of protocol treatment
i.e. after chemotherapy and after radiotherapy (if administered), as defined by
FDG-PET/CT
- To assess the safety and tolerability of the different BV containing regimens
- To assess the safety and tolerability of radiotherapy in the context of BrAVD
and BrECADD
- To assess efficacy in terms of PFS and OS
Exploratory objectives
- Response according to RECIL 2017
- To assess the degree of association between serum TARC level and FDG-PET
result both after one cycle of BrAVD among patients with pre-treatment TARC
elevation (see translational research in chapter 10)
- To identify markers that are potentially predictive for response or toxicity
or markers that can be used for treatment response monitoring (see
translational research chapter 10)
Study design
(see figure protocol chapter 4)
This is an international, open label, multi-center, single-arm phase II trial.
Patients fulfilling the inclusion criteria, will be centrally registered at
EORTC after written informed consent (IC) has been obtained.
All patients will receive 1 cycle of BrAVD followed by a FDG-PET with low-dose
CT scan (PET1). Further treatment will be based on the centrally revised PET1
results scored according to the Deauville 5 point score (DS) as follows:
1. If PET1-negative (Deauville score: 1-3): patients will receive an additional
5 cycles of BrAVD
2. If PET1-positive (Deauville score: 4-5): patients will switch treatment and
receive 6 cycles of BrECADD
Radiotherapy will be applied only to patients with residual PET positivity
(Deauville score 4 or 5) at the end of chemotherapy. Only sites of residual PET
positive disease will be irradiated.
Intervention
see study design
All patients will receive 1 cycle of BrAVD followed by a FDG-PET with low-dose
CT scan (PET1). Further treatment will be based on the centrally revised PET1
results scored according to the Deauville 5 point score (DS) as follows:
1. If PET1-negative (Deauville score: 1-3): patients will receive an additional
5 cycles of BrAVD
2. If PET1-positive (Deauville score: 4-5): patients will switch treatment and
receive 6 cycles of BrECADD
Radiotherapy will be applied only to patients with residual PET positivity
(Deauville score 4 or 5) at the end of chemotherapy. Only sites of residual PET
positive disease will be irradiated.
Study burden and risks
The diagnostic work-up and evaluation of treatment (before, during and after
protocol treatment) will differ only minimally from the standard of care (see
E).
The risk of Brentuximab-Vedotin mainly consists in the possible occurrence of
(largely reversible) polyneuropathy. Patients will be closely monitored during
treatment and adaptation of BV dose according to signs and symptoms of
polyneuropathy is extensively described in the protocol (see p 36 protocol).
BrECADD, the treatment for patients with a PET positive interim scan after 1
cycle of BrAVD will replace escBEACOPP which is currently standard of care for
patients in daily practice with a positive interim PET scan after 2 cycles of
ABVD. BrECADD has been shown to be equally effective but less toxic than
escBEACOPP.
Avenue E. Mounier 83/11
Brussel 1200
BE
Avenue E. Mounier 83/11
Brussel 1200
BE
Listed location countries
Age
Inclusion criteria
- Classical Hodgkin lymphoma, histologically proven, previously untreated
- Staged by FDG-PET with diagnostic-quality CT (i.v. contrast).
- Clinical stages according to Lugano 2014 and based on FDG/PET CT:
> Stage IIB with large mediastinal mass > 1/3 max transverse diameter thorax
and/or extranodal lesion(s)
> Stage III - IV
- Age >=18 and <=60
- WHO performance status 0-2 (Appendix C)
- Adequate organ function (for specification see 3.1.1 protocol page 24)
- Absence of any medical, psychological, familial, sociological or geographical
condition potentially hampering compliance with the study protocol and
follow-up schedule.
- Participation in translational research is mandatory and therefore patient
must consent for it.
- Negative pregnancy serum test < 72 h prior to 1st treatment (WOCBP)
- Willing to comply with birth control methods (protocol 3.1.1.) during the
study and 6 months after last treatment dose
- Written informed consent
Exclusion criteria
- Cerebral or meningeal disease (HL or any other etiology), including signs or
symptoms of Progressive Multifocal Leukoencephalopathy
- Symptomatic neurologic disease compromising normal activities of daily living
or requiring medications
- Sensory or motor peripheral neuropathy >= grade 2 according to CTCAE version
5.0
- Cardiovascular conditions (specifications see protocol 3.1.2 p 25)
- Poorly controlled diabetes mellitus (HbA1c > 7.5 % or a fasting blood sugar >
200 mg/dL).
- Any active systemic viral, bacterial, or fungal infection requiring systemic
antibiotics within 2 weeks prior to registration.
- Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg+
patients; HBsAg- HBcAb+/HBV DNA+ patients). Note: HBsAg-/HBV DNA - patients are
eligible; patients who are seropositive due to vaccination are eligible
- Concomitant or previous malignancies within the past 5 years, with the
exception of adequately treated carcinoma in situ of the cervix , non-melanoma
skin cancer.
- Previous treatment with anti CD30 antibodies
- Known hypersensitivity to any excipient contained in Brentuximab Vedotin
formulation and other study drugs.
- Concurrent anti-cancer treatment or use of any investigational agent(s)
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 |
|---|---|
| EU-CTR | CTIS2023-508478-27-00 |
| EudraCT | EUCTR2017-000498-35-NL |
| ClinicalTrials.gov | NCT03517137 |
| CCMO | NL67858.042.18 |