EORTC-1537-LYMG: Very early FDG-PET-response adapted targeted therapy for advanced Hodgkin lymphoma: a single-arm phase II study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

European Organisation For Research And Treatment Of Cancer

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Jul 2019 → ongoing

Decision date (initial)

2024-10-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Millennium Pharmaceuticals, Inc · European Organisation for Research and Treatment of Cancer (EORTC)

External identifiers

EU CT number

2023-508478-27-00

EudraCT number

2017-000498-35

ClinicalTrials.gov

NCT03517137

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy, Therapy

The main objective of this trial is to assess whether treatment adaptation based on a very early FDG-PET/CT 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.

Secondary objectives 5

1. To assess the rate of FDG-PET negativity (Deauville score 1-3) after 1 cycle of BrAVD
2. 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
3. To assess the safety and tolerability of the different BV containing regimens
4. To assess the safety and tolerability of radiotherapy in the context of BrAVD and BrECADD
5. To assess efficacy in terms of PFS and OS

Conditions and MedDRA coding

Advanced stage Hodgkin Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Previously untreated, histologically proven classical Hodgkin lymphoma
2. Staged by 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) (GHSG) - Stage III - IV
3. Participation in translational research is mandatory and therefore patient must consent to additional blood samples at multiple time points in the study. In addition, sufficient tissue must be available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block)
4. Age ≥18 and ≤60
5. WHO performance status 0-2
6. Patient demonstrates adequate organ function as defined in the protocol
7. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment
8. Patients of childbearing / reproductive potential should use two birth control methods, as defined by the investigator, from the time of signing the informed consent form, and throughout the entire study and for 6 months after the last dose of treatment
9. Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment
10. Absence of any medical, psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
11. Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations

Exclusion criteria 17

1. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy
2. Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
3. Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 5.0
4. Any of the following cardiovascular conditions or values: - within 6 months before registration
5. A left-ventricular ejection fraction <50%
6. New York Heart Association (NYHA) Class III or IV heart failure
7. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
8. symptomatic coronary heart disease (stable angina pectoris is allowed)
9. severe uncontrolled hypertension defined as blood pressure (BP) >150/100 mmHg despite optimal antihypertensive treatment - within 2 years before registration
10. Myocardial infarction
11. Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 % or a fasting blood sugar > 200 mg/dL)
12. Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to registration
13. Known HIV infection, chronic active hepatitis C, HBV positivity (HBsAg + patients; HBsAg -/HBcAb+/HBV DNA+ patients)
14. Concomitant or previous malignancies within the past 5 years with the exception of adequately treated carcinoma in situ of the cervix, nonmelanoma skin cancer
15. Previous treatment with anti CD30 antibodies
16. Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs
17. Concurrent anti-cancer treatment or use of any investigational agent(s)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Modified progression-free survival rate at 2 years after start of treatment (2yr-mPFS for each patient). 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; death from any cause.

Secondary endpoints 6

1. FDG-PET result (positive/negative) after 1 cycle of BrAVD (central assessment)
2. 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
3. Progression-free survival (where progression, relapse and death from any cause are considered events)
4. Overall survival
5. Safety and tolerability
6. Response according to RECIL 2017

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

European Organisation For Research And Treatment Of Cancer

Sponsor organisation

European Organisation For Research And Treatment Of Cancer

Address

Emmanuel Mounierlaan 83 Bus 11

City

Sint-Lambrechts-Woluwe

Postcode

1200

Country

Belgium

Scientific contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Stéphanie Kromar

Public contact point

Organisation

European Organisation For Research And Treatment Of Cancer

Contact name

Vassilis Golfinopoulos

Third parties 2

Locations

7 EU/EEA countries · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications