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

NCT03517137 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: EORTC-1537-LYMG
• Study Type: interventional
• Target: 150
• Locations: 7 countries
• Sites: 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.

Conditions

Advanced Hodgkin Lymphoma

Keywords

advanced Hodgkin lymphoma; brentuximab vedotin; phase 2

Outcome Measures

Primary Outcomes (1)

• Modified Progression-free Survival (mPFS) Rate at 2 Years

  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 than 1 missed cycle, including radiotherapy on PET positive lesions if administered * Death due to any cause

  2 years from the date of treatment start

Secondary Outcomes (3)

• Proportion of Patients With a Negative FDG-PET

  At day 22 to 23 from start of treatment (day 1 = date of start of treatment)

• Progression-free Survival (PFS) Rate at 2 Years

  2 years from the date of treatment start

• Overall Survival Rate at 2 Years

  2 years from the date of treatment start

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Brentuximab Vedotin; Drug: Adriamycin; Drug: Vinblastine; Drug: Dacarbazine; Drug: Etoposide; Drug: Cyclophosphamide; Radiation: Radiation Therapy

Interventions

Brentuximab Vedotin 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)

Treatment

Adriamycin 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)

Treatment

Vinblastine 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)

Treatment

Dacarbazine 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)

Treatment

Etoposide 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)

Treatment

Cyclophosphamide 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)

Treatment

Radiation Therapy 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.

Treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (16)

ZNA Stuivenberg

Antwerp, 2060, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

University Hospitals Copenhagen - Rigshospitalet

Copenhagen, 2100, Denmark

Location

Amsterdam UMC - Locatie AMC

Amsterdam, 1105, Netherlands

Location

Deventer Ziekenhuis

Deventer, 7400, Netherlands

Location

University Medical Center Groningen

Groningen, 9713, Netherlands

Location

Medisch Centrum Leeuwarden-Zuid

Leeuwarden, 8934, Netherlands

Location

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

Leidschendam, 2262, Netherlands

Location

Radboudumc - Radboud University Medical Center Nijmegen

Nijmegen, 6525, Netherlands

Location

Erasmus MC

Rotterdam, 3015, Netherlands

Location

Maria Sklodowska Curie National Institute of Oncology - National Research Institute

Warsaw, 02781, Poland

Location

Instituto Portugues De Oncologia - Francisco Gentil - Centro De Lisboa

Lisbon, 1099, Portugal

Location

National Cancer Institute

Bratislava, 833, Slovakia

Location

Hospital Duran i Reynals (Institut Catala D'Oncologia)

L'Hospitalet de Llobregat, 08908, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

Related Publications (1)

• 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.

  PMID: 40135712 DERIVED

MeSH Terms

Interventions

Brentuximab Vedotin; Doxorubicin; Vinblastine; Dacarbazine; Etoposide; Cyclophosphamide; Radiotherapy

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Therapeutics

Results Point of Contact

• Title: Catherine Fortpied
• Organization: EORTC

catherine.fortpied@eortc.org

+32 2 774 1681

Study Officials

• Martin Hutchings

  Past Chair EORTC Lymphoma Group

  PRINCIPAL INVESTIGATOR

• Wouter Plattel

  Active Member EORTC Lymphoma Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2018
• First Posted: May 7, 2018
• Study Start: August 1, 2019
• Primary Completion: August 28, 2023
• Study Completion (Estimated): November 16, 2026
• Last Updated: August 11, 2025
• Results First Posted: August 11, 2025

Record last verified: 2025-08

Locations

PL (1); BE (3); PT (1); NL (7); SL (1); ES (2); DK (1)