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

NCT ID: NCT03517137

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2026-11-16

Brief Summary

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.

Detailed Description

This single-arm phase II study investigates the value of early FDG-PET-response adapted BV-based therapy for advanced HL. All patients will receive one cycle of BrAVD followed by an FDG-PET/CT. Patients with a negative early FDG-PET(Deauville score 1-3) will continue with five more BrAVD cycles (total six cycles) while patients with a positive FDG-PET should shift to six cycles of BrECADD.

The hypothesis is that the efficacy will be comparable to the efficacy of BEACOPPesc and BrECADD, while using the intensive chemotherapy regimen only for those patients who do not achieve a negative FDG-PET after one cycle.

The choice to assess the treatment sensitivity by PET after a single cycle of BrAVD is based on results from a recent international multicenter study comparing FDG-PET/CT after one and two cycles of ABVD chemotherapy in HL. There is no reason to suspect that FDG-PET1 should be less prognostic after BrAVD than after ABVD.

With this trial, the investigators believe they can add important information about the optimal treatment of BV-containing first-line treatment for advanced HL, and thus answer important therapeutic questions that are likely to otherwise remain unanswered even after the Echelon-1 and HD21 trials reach mature results. This relatively large single-arm phase II trial of 150 patients will allow a meaningful comparison with the BrAVD and BrECADD regimens based on modified progression-free survival (primary endpoint) and progression-free survival (secondary endpoint) respectively.

Conditions

Advanced Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Group Type: EXPERIMENTAL

Brentuximab Vedotin

Intervention Type: DRUG

For PET positive (score of 4-5 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.8 mg/kg on day 1, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.2 mg/kg on day 1 and 15, every 4 weeks (5 cycles)

Adriamycin

Intervention Type: DRUG

For PET positive (score of 4-5 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 40 mg/m² on day 2, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 25 mg/m² on day 1 and 15, every 4 weeks (5 cycles)

Vinblastine

Intervention Type: DRUG

For PET negative (score of 1-3 following Deauville Criteria) patients: Vinblastine is administered as an IV infusion over a period of 15 minutes at 6mg/m² on day 1 and 15, every 4 weeks (5 cycles)

Dacarbazine

Intervention Type: DRUG

For PET positive (score of 4-5 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 250 mg/m² on day 3 and 4, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 375 mg/m² on day 1 and 15, every 4 weeks (5 cycles)

Etoposide

Intervention Type: DRUG

For PET positive (score of 4-5 following Deauville Criteria) patients: Etoposide is administered as an IV infusion over a period of 60 minutes at 150 mg/m² on day 2,3 and 4, every 3 weeks (6 cycles)

Cyclophosphamide

Intervention Type: DRUG

For PET positive (score of 4-5 following Deauville Criteria) patients: Cyclophosphamide is administered as an IV infusion over a period of 30 minutes at 1250 mg/m² on day 2, every 3 weeks (6 cycles)

Radiation Therapy

Intervention Type: RADIATION

Patients with residual lymphoma mass(es) showing metabolic activity of Deauville score 4 or 5 after completion of chemotherapy will be offered consolidation radiotherapy.

Interventions

Brentuximab Vedotin

For PET positive (score of 4-5 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.8 mg/kg on day 1, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Brentuximab vedotin is administered as an IV infusion over a period of 30 minutes at 1.2 mg/kg on day 1 and 15, every 4 weeks (5 cycles)

Intervention Type: DRUG

Adriamycin

For PET positive (score of 4-5 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 40 mg/m² on day 2, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Adriamycin is administered as an IV infusion over a period of 15 minutes at 25 mg/m² on day 1 and 15, every 4 weeks (5 cycles)

Intervention Type: DRUG

Vinblastine

For PET negative (score of 1-3 following Deauville Criteria) patients: Vinblastine is administered as an IV infusion over a period of 15 minutes at 6mg/m² on day 1 and 15, every 4 weeks (5 cycles)

Intervention Type: DRUG

Dacarbazine

For PET positive (score of 4-5 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 250 mg/m² on day 3 and 4, every 3 weeks (6 cycles); For PET negative (score of 1-3 following Deauville Criteria) patients: Dacarbazine is administered as an IV infusion over a period of 60 minutes at 375 mg/m² on day 1 and 15, every 4 weeks (5 cycles)

Intervention Type: DRUG

Etoposide

For PET positive (score of 4-5 following Deauville Criteria) patients: Etoposide is administered as an IV infusion over a period of 60 minutes at 150 mg/m² on day 2,3 and 4, every 3 weeks (6 cycles)

Intervention Type: DRUG

Cyclophosphamide

For PET positive (score of 4-5 following Deauville Criteria) patients: Cyclophosphamide is administered as an IV infusion over a period of 30 minutes at 1250 mg/m² on day 2, every 3 weeks (6 cycles)

Intervention Type: DRUG

Radiation Therapy

Patients with residual lymphoma mass(es) showing metabolic activity of Deauville score 4 or 5 after completion of chemotherapy will be offered consolidation radiotherapy.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• Previously untreated, histologically proven classical Hodgkin lymphoma;
• 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)
• Stage III - IV
• Consent to participation in translational research:
• Archival tumor tissue available (15 blank formalin fixed paraffin embedded tissue samples mounted on APES slides or a tissue block).
• Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the first dose of study treatment.
• Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last dose of treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1 percent per year) when used consistently and correctly.
• 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.
• 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
• Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria

• Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of Progressive Multifocal Leukoencenphalopathy
• Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
• Sensory or motor peripheral neuropathy greater than or equal to grade 2 according to CTCAE version 4.0
• Any of the following cardiovascular conditions or values:

within 6 months before registration:

• A left-ventricular ejection fraction <50 percent (at registration)
• New York Heart Association (NYHA) Class III or IV heart failure.
• 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
• symptomatic coronary heart disease (stable angina pectoris is allowed)
• severe uncontrolled hypertension within 2 years before registration
• Myocardial infarction
• Patients with poorly controlled diabetes mellitus (HbA1c > 7.5 percent 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 , nonmelanoma skin cancer.
• Previous treatment with anti CD30 antibodies
• Known hypersensitivity to any excipient contained in Brentuximab Vedotin formulation and other study drugs. Refer to Summary Product Characteristics for list of excipients.
• Concurrent anti-cancer treatment or use of any investigational agent(s)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Martin Hutchings

Role: PRINCIPAL_INVESTIGATOR

Past Chair EORTC Lymphoma Group

Wouter Plattel

Role: PRINCIPAL_INVESTIGATOR

Active Member EORTC Lymphoma Group

Locations

ZNA Stuivenberg

Antwerp, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

U.Z. Leuven - Campus Gasthuisberg

Leuven, , Belgium

University Hospitals Copenhagen - Rigshospitalet

Copenhagen, , Denmark

Amsterdam UMC - Locatie AMC

Amsterdam, , Netherlands

Deventer Ziekenhuis

Deventer, , Netherlands

University Medical Center Groningen

Groningen, , Netherlands

Medisch Centrum Leeuwarden-Zuid

Leeuwarden, , Netherlands

Haaglanden Medisch Centrum (HMC) - Haaglanden MC - locatie Antoniushove

Leidschendam, , Netherlands

Radboudumc - Radboud University Medical Center Nijmegen

Nijmegen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Maria Sklodowska Curie National Institute of Oncology - National Research Institute

Warsaw, , Poland

Instituto Portugues De Oncologia - Francisco Gentil - Centro De Lisboa

Lisbon, , Portugal

National Cancer Institute

Bratislava, , Slovakia

Hospital Duran i Reynals (Institut Catala D'Oncologia)

L'Hospitalet de Llobregat, , Spain

Complejo Hospitalario de Navarra

Pamplona, , Spain

Countries

Belgium; Denmark; Netherlands; Poland; Portugal; Slovakia; Spain

References

Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

Reference Type: DERIVED

PMID: 40135712 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

EORTC-1537-LYMG

Identifier Type: -

Identifier Source: org_study_id