Efficacy and Tolerability of N-AVD compared to BrECADD in patients with advanced Hodgkin Lymphoma (N-BRAVE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Polska Grupa Badawcza Chloniakow

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medical Research Agency (PL. Agencja Badań Medycznych)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate the non-inferiority of the N-AVD regimen compared with the BrECADD regimen in terms of complete metabolic response (CMR), assessed by PET/CT, as first-line treatment in patients with advanced Hodgkin lymphoma.

Secondary objectives 7

1. To compare progression-free survival (PFS) between patients treated with the N-AVD regimen and those treated with the BrECADD regimen.
2. To compare event-free survival (EFS) between patients treated with the N-AVD regimen and those treated with the BrECADD regimen.
3. To compare overall survival (OS) between the N-AVD and BrECADD treatment arms.
4. To evaluate and compare treatment-related morbidity (TRMB) and the safety profiles of the N-AVD and BrECADD regimens.
5. To assess and compare health-related quality of life (QoL) in patients treated with the N-AVD and BrECADD regimens.
6. To evaluate and compare the depth of treatment response by assessing minimal residual disease using circulating tumor DNA (ctDNA) and thymus and activation-regulated chemokine (TARC).
7. To assess gonadal recovery following treatment.

Conditions and MedDRA coding

Hodgkin lymphoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients must meet all inclusion criteria according to the National Health Fund Drug Program B.77, points 1.1 and 1.2.2.
2. ECOG performance status 0–2.
3. Histologically confirmed CD30-positive, newly diagnosed classical Hodgkin lymphoma in stage IIB with risk factors (i.e. bulky disease ≥10 cm or ≥1/3 of the maximum transverse diameter of the chest, or extranodal involvement) or stage III or IV according to the Ann Arbor classification.
4. Age ≥18 years.
5. Written informed consent to participate in the clinical trial.
6. In women of childbearing potential (WOCBP): a negative highly sensitive serum pregnancy test (β-hCG) during screening prior to randomization, and agreement to use a highly effective contraceptive method during the study treatment period and for 6 months after the last dose of protocol treatment. Women are not considered of childbearing potential if they are post-menopausal (defined as at least 12 consecutive months of spontaneous amenorrhea without another medical cause) or permanently sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or bilateral tubal occlusion). In male participants of reproductive potential: agreement to use a condom during sexual intercourse and to ensure that a female partner of childbearing potential uses a highly effective contraceptive method, or to practice true sexual abstinence consistent with usual lifestyle, during the study treatment period and for 6 months after the last dose of protocol treatment

Exclusion criteria 13

1. Age below 18 years.
2. Diagnosis of non-classical Hodgkin lymphoma or composite lymphoma.
3. ECOG performance status greater than 2.
4. Previous treatment of Hodgkin lymphoma, except for corticosteroids.
5. Pregnancy or breastfeeding.
6. Presence of another malignancy in active form or diagnosed within less than 5 years after achieving complete remission.
7. Uncontrolled diabetes mellitus.
8. Cardiac failure NYHA class greater than II or left ventricular ejection fraction below 45%.
9. Liver failure defined as bilirubin >1.5 × upper limit of normal (ULN) or AST/SGOT >5 × ULN, if not related to lymphoma involvement, and Gilbert’s syndrome.
10. Active infection with HIV, HBV, HCV, or CMV. In case of hepatitis B with positive anti-HBc antibodies, HBV DNA PCR testing and initiation of prophylactic treatment are required in consultation with an infectious disease specialist.
11. Known hypersensitivity to any of the medicinal products used in the study.
12. Inability of the patient to provide written informed consent.
13. Active autoimmune disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete metabolic response (CMR) rate assessed by PET/CT 6–8 weeks after completion of chemotherapy.

Secondary endpoints 7

1. Progression-Free Survival (PFS), assessed during the whole study period.
2. Event-Free Survival (EFS), assessed during the whole study period.
3. Quality of life (QoL) assessed using the EORTC QLQ-HL27 questionnaire, evaluated before treatment, after 2 cycles of chemotherapy, at the end of chemotherapy, and at each follow-up visit.
4. Treatment-related morbidity (TRMB), assessed as the frequency of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE), evaluated after each cycle of chemotherapy.
5. Gonadal recovery assessed by follicle-stimulating hormone (FSH) measurement, evaluated 1 year after completion of chemotherapy.
6. Negative residual disease status assessed by circulating tumor DNA (ctDNA) concentration and thymus and activation-regulated chemokine (TARC) concentration, evaluated after 2 chemotherapy cycles and at the end of chemotherapy (at the time of PET assessment).
7. Overall survival (OS), assessed during the whole study period.

Investigational products

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

Test 4

Comparator 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Polska Grupa Badawcza Chloniakow

Sponsor organisation

Polska Grupa Badawcza Chloniakow

Address

Ul. Mariana Smoluchowskiego 17

City

Gdansk

Postcode

80-214

Country

Poland

Scientific contact point

Organisation

Polska Grupa Badawcza Chloniakow

Contact name

Project Manager

Public contact point

Organisation

Polska Grupa Badawcza Chloniakow

Contact name

Project Manager

Locations

1 EU/EEA country · 15 investigational sites

By country

Investigational sites

Results and documents

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

Documents 24 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