Very early FDG-PET-response adapted targeted therapy for advanced Hodgkin lymphoma: a single-arm phase II study

Phase 2

Recruiting

Conditions: Hodgkin's disease
malignant lymphoma
10025319

Registration Number: NL-OMON50149

Lead Sponsor: European Organisation for Research in Treatment of Cancer (EORTC)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 38

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)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Modified progression-free survival rate at 2 years after start of treatment<br /><br>(2yr-mPFS).<br /><br><br /><br>The following are considered events for the primary endpoint:<br /><br># progression/relapse;<br /><br># start of new treatment for cHL when not in CR after completing protocol<br /><br>treatment (including radiotherapy)<br /><br># death from any cause. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Patients with negative FDG-PET after 1 cycle of BrAVD (central assessment)<br /><br>- Response rate according to Lugano Criteria at end of protocol treatment i.e.<br /><br>after chemotherapy and after radiotherapy (if administered),<br /><br>- Progression-free survival (where progression, relapse and death from any<br /><br>cause are considered events).<br /><br>- Overall survival<br /><br>- Safety and tolerability<br /><br><br /><br>Exploratory:<br /><br>- Response rate according to RECIL 2017<br /><br>- To assess the degree of association between serum TARC level and FDG-PET<br /><br>result both after one cycle of BrAVD among patients with pre-treatment TARC<br /><br>elevation (see translational research in chapter 10)<br /><br>- To identify markers that are potentially predictive for response or toxicity<br /><br>or markers that can be used for treatment response monitoring (see<br /><br>translational research chapter 10)</p><br>