Contact information
Type
Scientific
Primary contact
Prof Volker Diehl
ORCID ID
Contact details
German Hodgkin's Lymphoma Study Group
Herderstr. 52-54
Cologne
50924
Germany
+49/221/478-3557 (-3558)
dhsg@biometrie.uni-koeln.de
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
HD15
Study hypothesis
Primary aim:
Reduction of toxicity, de-escalation of chemotherapy while maintaining high freedom from treatment failure (FFTF) and overall survival (OS) rates.
Secondary aims:
Assess the influence of erythropoietin on the quality of life and the effect of FDG-PET on prognosis.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Patient information sheet can be found at http://www.lymphome.de/en/Groups/GHSG/Protocols/HD15/Patient-Information.pdf
Condition
Hodgkin's disease
Intervention
In this trial three combinations of chemotherapy are compared in a randomised, controlled trial (open-label). In addition patients in every arm are randomly assigned to receive erythropoetin or placebo (double-blind). Restaging with PET is not allocated in a randomised fashion:
Arm A:
1. 8 x erythropoietin, cyclophosphamide, adriamycin, etoposide, vincristine, bleomycin, procarbazine (BEACOPP) (escalated)
2. Erythropoetin/placebo
3. 30 Gy involved field radiotherapy if partial remission after chemotherapy and PET is positive
Arm B:
1. 6 x BEACOPP (escalated)
2. Erythropoetin/placebo
3. 30 Gy involved field radiotherapy if partial remission after chemotherapy and PET is positive
Arm C:
1. 8 x BEACOPP-14
2. Erythropoetin/placebo
3. 30 Gy involved field radiotherapy if partial remission after chemotherapy and PET is positive
Intervention type
Drug
Phase
Not Specified
Drug names
Erythropoietin, cyclophosphamide, adriamycin, etoposide, vincristine, bleomycin, procarbazine (BEACOPP)
Primary outcome measures
Freedom from treatment failure (FFTF).
Secondary outcome measures
Impact of erythropoetin on quality of life and prognostic significance of FDG-PET.
Overall trial start date
01/01/2003
Overall trial end date
01/01/2008
Reason abandoned
Eligibility
Participant inclusion criteria
Chemotherapy:
1. Histologically confirmed Hodgkin's disease
2. Stage IIB and massive mediastinal involvement (tumour one third or more of the maximum intrathoracic diameter) and/or extranodal involvement, stage III, and stage IV
3. No prior therapy for Hodgkin's disease
4. Age: 18 - 60 years
5. No major organ dysfunction
6. Life expectancy greater than 3 months
7. Written informed consent
PET:
1. Chemotherapy according to the HD15-protocol
2. Response to chemotherapy
3. Partial response with residual disease of at least 2.5 cm maximum diameter
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
400
Participant exclusion criteria
Chemotherapy:
1. Incomplete staging
2. Major organ dysfunction:
2.1. Chronic obstructive pulmonary disease (COPD) with respiratory insufficiency
2.2. Symptomatic coronary heart disease (CHD)
2.3. Cardiomyopathy or heart failure (ejection fraction less than 50%)
2.4. Severe hypertension
2.5. Non-treatable infections
2.6. White blood count less than 3000/mm^3 or platelets less than 100,000/mm^3 if not related to bone marrow involvement
2.7. Creatinine clearance less than 60 ml/min
2.8. Bilirubin greater than 2 mg/dl if not related to Hodgkin's disease
2.9. Glutamic oxaloacetic transaminase (GOT)/aspartate aminotransferase (AST) greater than 100 U/l if not related to Hodgkin's disease
2.10. Glutamic pyruvic transaminase (GPT)/alanine aminotransferase (ALT) greater than 100 U/l if not related to Hodgkin's disease
2.11. Human immunodeficiency virus (HIV)-infection
3. Composite lymphoma
4. Prior chemotherapy or radiotherapy
5. Any history of another malignancy in the last 5 years (except for cervical carcinoma in situ and fully resected melanoma TNMpT1)
6. Pregnancy or breastfeeding
7. World Health Organisation (WHO) performance status greater than 2
8. Long term use of corticosteroids (e.g. for arthritis) or antineoplastic substances (e.g. methotrexate)
9. Expected non-compliance
10. Current therapy for epilepsy
11. Intolerabilities against study drugs
PET:
1. Diabetes mellitus
2. Elevated blood glucose (greater than 130 mg/dl)
3. Massive bone involvement (endangering stability)
Recruitment start date
01/01/2003
Recruitment end date
01/01/2008
Locations
Countries of recruitment
Germany
Trial participating centre
German Hodgkin's Lymphoma Study Group,
Cologne
50924
Germany
Sponsor information
Organisation
German Hodgkin's Lymphoma Study Group (Germany)
Sponsor details
Herderstr. 52-54
Cologne
50924
Germany
+49 (0)221 478-3557 (-3558)
dhsg@biometrie.uni-koeln.de
Sponsor type
Research organisation
Website
Funders
Funder type
Charity
Funder name
Deutsche Krebshilfe (Germany)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2008 results in: http://www.ncbi.nlm.nih.gov/pubmed/18757777
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22480758
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24799482
Publication citations
-
Results
Kobe C, Dietlein M, Franklin J, Markova J, Lohri A, Amthauer H, Klutmann S, Knapp WH, Zijlstra JM, Bockisch A, Weckesser M, Lorenz R, Schreckenberger M, Bares R, Eich HT, Mueller RP, Fuchs M, Borchmann P, Schicha H, Diehl V, Engert A, Positron emission tomography has a high negative predictive value for progression or early relapse for patients with residual disease after first-line chemotherapy in advanced-stage Hodgkin lymphoma., Blood, 2008, 112, 10, 3989-3994, doi: 10.1182/blood-2008-06-155820.
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Results
Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, Zijlstra J, Král Z, Fuchs M, Hallek M, Kanz L, Döhner H, Dörken B, Engel N, Topp M, Klutmann S, Amthauer H, Bockisch A, Kluge R, Kratochwil C, Schober O, Greil R, Andreesen R, Kneba M, Pfreundschuh M, Stein H, Eich HT, Müller RP, Dietlein M, Borchmann P, Diehl V, , , , Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial., Lancet, 2012, 379, 9828, 1791-1799, doi: 10.1016/S0140-6736(11)61940-5.
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Results
Kobe C, Kuhnert G, Kahraman D, Haverkamp H, Eich HT, Franke M, Persigehl T, Klutmann S, Amthauer H, Bockisch A, Kluge R, Wolf HH, Maintz D, Fuchs M, Borchmann P, Diehl V, Drzezga A, Engert A, Dietlein M, Assessment of tumor size reduction improves outcome prediction of positron emission tomography/computed tomography after chemotherapy in advanced-stage Hodgkin lymphoma., J. Clin. Oncol., 2014, 32, 17, 1776-1781, doi: 10.1200/JCO.2013.53.2507.