NCT03517137: COBRA

Very Early PET-response Adapted Targeted Therapy for Advanced Hodgkin Lymphoma: a Single -Arm Phase II Study

Active, enrolled Phase 2 Results posted Last updated 11 August 2025

What this trial tests

Phase 2 trial testing Brentuximab Vedotin in Advanced Hodgkin Lymphoma in 150 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

1 August 2019

Primary endpoint
28 August 2023

16 November 2026

Quick facts

Lead sponsor	European Organisation for Research and Treatment of Cancer - EORTC
Phase	Phase 2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	150
Start date	1 August 2019
Primary completion	28 August 2023
Estimated completion	16 November 2026
Sites	16 locations across Denmark, Netherlands, Slovakia, Belgium, Poland, Portugal, Spain

Drugs / interventions tested

• Brentuximab Vedotin — full drug profile →
• Adriamycin
• Vinblastine
• Dacarbazine (dacarbazine) — full drug profile →
• Etoposide (etoposide) — full drug profile →
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Radiation Therapy

Conditions studied

• Advanced Hodgkin Lymphoma — all drugs for Advanced Hodgkin Lymphoma →

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC — full company profile →

Who can join

Adults 18 to 60, any sex, with Advanced Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Modified Progression-free Survival (mPFS) Rate at 2 Years Primary · 2 years from the date of treatment start

Modified PFS (mPFS) is defined as the time interval between the date of treatment start and the date of the first of: * Progressive disease (PD) * Start of new treatment for Classical Hodgkin Lymphoma (cHL) when not in Complete Response at the end of protocol treatment; in this case, the date of mPFS is the date of the FDG-PET/CT scan at the end of protocol treatment. Switching therapy prior to end of protocol treatment for reasons other than Progressive Disease is not considered an event for mPFS. "End of protocol treatment" refers to completion of the planned protocol treatment with no more

Group	Value	95% CI
Evaluable Population	89.5	85.7 – 92.4

Proportion of Patients With a Negative FDG-PET Secondary · At day 22 to 23 from start of treatment (day 1 = date of start of treatment)

It will be assessed how many patients have a negative FDG-PET image when taken at the end of their first cycle of BrAVD. The BrAVD cycle lasts 4 weeks.

Group	Value	95% CI
Treatment	90
Treatment	60

Progression-free Survival (PFS) Rate at 2 Years Secondary · 2 years from the date of treatment start

Progression-free survival

Group	Value	95% CI
Evaluable Population	89.5	83.3 – 93.6

Overall Survival Rate at 2 Years Secondary · 2 years from the date of treatment start

Overall survival

Group	Value	95% CI
Evaluable Population	100

Adverse events — posted to ClinicalTrials.gov

Time frame: Each observed adverse event was to be reported as of 4 weeks within registration until 28 days after start of last cycle of chemotherapy. If radiotherapy given, assessment of adverse events should be done until 8 weeks after completion. Related adverse events should be assessed as of 3 months after the end of treatment until 5 years after end of treatment. All adverse events must be followed until resolution or stabilization. Survival status: assessed until 5 years after end of treatment.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment

Serious: 45/150 (30%)

Deaths: 0/150

Serious adverse events (59 terms)

Reaction	System	Treatment
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	—
CONSTIPATION	Gastrointestinal disorders	—
PNEUMOCYSTIS JIROVECII PNEUMONIA	Infections and infestations	—
ANAEMIA	Blood and lymphatic system disorders	—
NEUTROPENIA	Blood and lymphatic system disorders	—
VOMITING	Gastrointestinal disorders	—
PYREXIA	General disorders	—
INFECTION	Infections and infestations	—
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	—
NAUSEA	Gastrointestinal disorders	—
NEUTROPENIC COLITIS	Gastrointestinal disorders	—
STOMATITIS	Gastrointestinal disorders	—
DEVICE RELATED INFECTION	Infections and infestations	—
THROMBOPHLEBITIS SEPTIC	Infections and infestations	—
PLATELET COUNT DECREASED	Investigations	—
PERIPHERAL MOTOR NEUROPATHY	Nervous system disorders	—
THROMBOCYTOPENIA	Blood and lymphatic system disorders	—
CARDIAC TAMPONADE	Cardiac disorders	—
PERICARDIAL EFFUSION	Cardiac disorders	—
PRINZMETAL ANGINA	Cardiac disorders	—
ABDOMINAL PAIN	Gastrointestinal disorders	—
ILEUS	Gastrointestinal disorders	—
INTESTINAL PSEUDO-OBSTRUCTION	Gastrointestinal disorders	—
PANCREATITIS ACUTE	Gastrointestinal disorders	—
MUCOSAL INFLAMMATION	General disorders	—

Other adverse events (245 terms — click to expand)

Reaction	System	Treatment
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	—
NAUSEA	Gastrointestinal disorders	—
CONSTIPATION	Gastrointestinal disorders	—
NEUTROPHIL COUNT DECREASED	Investigations	—
FATIGUE	General disorders	—
ANEMIA	Blood and lymphatic system disorders	—
VOMITING	Gastrointestinal disorders	—
PERIPHERAL MOTOR NEUROPATHY	Nervous system disorders	—
ABDOMINAL PAIN	Gastrointestinal disorders	—
DIARRHEA	Gastrointestinal disorders	—
BONE PAIN	Musculoskeletal and connective tissue disorders	—
INSOMNIA	Psychiatric disorders	—
MUCOSITIS ORAL	Gastrointestinal disorders	—
FEVER	General disorders	—
MYALGIA	Musculoskeletal and connective tissue disorders	—
DYSGEUSIA	Nervous system disorders	—
HYPERTENSION	Vascular disorders	—
WHITE BLOOD CELL DECREASED	Investigations	—
PLATELET COUNT DECREASED	Investigations	—
WEIGHT LOSS	Investigations	—
ALANINE AMINOTRANSFERASE INCREASED	Investigations	—
ANOREXIA	Metabolism and nutrition disorders	—
BACK PAIN	Musculoskeletal and connective tissue disorders	—
HEADACHE	Nervous system disorders	—
PARESTHESIA	Nervous system disorders	—
DYSPNEA	Respiratory, thoracic and mediastinal disorders	—
ALOPECIA	Skin and subcutaneous tissue disorders	—
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	—
WEIGHT GAIN	Investigations	—
DIZZINESS	Nervous system disorders	—
HYPERHIDROSIS	Skin and subcutaneous tissue disorders	—
PRURITUS	Skin and subcutaneous tissue disorders	—
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	—
COUGH	Respiratory, thoracic and mediastinal disorders	—
MALAISE	General disorders	—
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	—
DRY EYE	Eye disorders	—
HYPOKALEMIA	Metabolism and nutrition disorders	—
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	—
DRY SKIN	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: FEBRILE NEUTROPENIA, CONSTIPATION, PNEUMOCYSTIS JIROVECII PNEUMONIA, ANAEMIA, NEUTROPENIA, VOMITING, PYREXIA, INFECTION.

Data from ClinicalTrials.gov NCT03517137 adverse events section.

Sponsor's own description

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 Hodgkin Lymphoma (HL) patients treated with brentuximab vedotin (BV)-containing regimens.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Advances in Hodgkin Lymphoma Treatment: From Molecular Biology to Clinical Practice.
   Benevolo Savelli C, Bisio M, Legato L, Fasano F, et al · · 2024 · cited 14× · PMID 38791909 · DOI 10.3390/cancers16101830
2. Current advances in Hodgkin's lymphoma.
   Vadakara J, Andrick B. · · 2019 · cited 4× · PMID 30993260 · DOI 10.1016/j.cdtm.2019.02.003
3. Very early [<sup>18</sup>F]FDG-PET-guided targeted therapy in untreated advanced-stage classic Hodgkin lymphoma (EORTC-1537-COBRA): primary results of a single-arm, multicentre, phase 2 trial.
   Hutchings M, Diepstra A, Sureda Balari A, Carvalho S, et al · · 2026 · PMID 42069408 · DOI 10.1016/s2352-3026(26)00068-2