Clinical Trial Results:
Pilot trial for the therapy optimisation of children and adolescents with Hodgkin's lymphoma Evaluation of safety of the chemotherapy regimen VECOPA in patients with intermediate or advanced stage disease (Pilotstudie zur Therapieoptimierungsstudie für den Morbus Hodgkin bei Kindern und Jugendlichen. Prüfung der Verträglichkeit der Chemotherapiekombination VECOPA bei Patienten der Therapiegruppen 2 und 3)

Trial information Top of page
Trial identification
Sponsor protocol code	GPOH-HD 2002 Pilot / VECOPA
Additional study identifiers
ISRCTN number	-
US NCT number	-
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	MLU Halle-Wittenberg
Sponsor organisation address	Magdeburgerstrasse 8, Halle (Saale), Germany,
Public contact	Prof Dr. D. Körholz, MLU Halle-Wittenberg, 0049 345-5572388, dieter.koerholz@medizin.uni-halle.de
Scientific contact	Prof Dr. D. Körholz , MLU Halle-Wittenberg, 0049 345-5572388, dieter.koerholz@medizin.uni-halle.de
Sponsor organisation name	University Leipzig
Sponsor organisation address	Ritterstrasse 26, Leipzig, Germany,
Public contact	Prof Dr. D. Körholz MLU Halle-Wittenberg Ernst-Grube-Strasse 40, 06120 Halle (Saale), Leipzig University, 0049 345-5572388, dieter.koerholz@medizin.uni-halle.de
Scientific contact	Prof Dr. D. Körholz MLU Halle-Wittenberg Ernst-Grube-Strasse 40, 06120 Halle (Saale), Leipzig University , 0049 345-5572388, dieter.koerholz@medizin.uni-halle.de
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	11 Feb 2014
Is this the analysis of the primary completion data?	Yes
Primary completion date	31 Aug 2013
Global end of trial reached?	Yes
Global end of trial date	31 Aug 2013
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	Feasibility and safety of VECOPA instead of standard COPP in male patients with intermediate or advanced stage Hodgkin's lymphoma (Kann bei Jungen in den Therapiegruppen 2 und 3 die Kombination VECOPA anstelle des bisher üblichen COPP mit vertretbarer Toxizität eingesetzt werden?)
Protection of trial subjects	Patients were closeyl monitored with regard to safety during the course of the study including systematic AE documentation.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	27 May 2005
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Germany: 15
Worldwide total number of subjects	15
EEA total number of subjects	15
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	1
Adolescents (12-17 years)	14
Adults (18-64 years)	0
From 65 to 84 years	0
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	-
Pre-assignment
Screening details	Only subjects who met all inclusion criteria, but none of the exclusion criteria were enrolled.
Period 1
Period 1 title	Overall trial (overall period)
Is this the baseline period?	Yes
Allocation method	Not applicable
Blinding used	Not blinded
Blinding implementation details	No blinding.
Arms
Arm title	VECOPA
Arm description	All patients received two induction cycles of OEPA (standard treatment). Patients with intermediate or advanced stage disease received one or two cycles of VECOPA (experimental). OEPA cycles consisted of vincristine 1.5 mg/m 2 intravenously (i.v.) on days 1, 8 and 15; etoposide 125 mg/m 2 i.v. on days 3 – 8; prednisone 60 mg/m 2 orally (p.o.) on days 1 – 15; and doxorubicin 40 mg/m 2 i.v. on days 1 and 15 VECOPA consisted of Etoposid 150 mg/m² i.v. days 1-3; Adriamycin 25mg/m²/i.v. day 21; Vinblastin 6 mg/m² i.v. days 1 and 21; Vincristin 1.5 mg/m2 i.v. days 8 and 29; Cyclophosphamide 1250 mg/m2 i.v. days 1 and 21;Prednisone 40 mg/m2 p.o. days 1-14 and 21-34
Arm type	Experimental
Investigational medicinal product name	Adriblastin
Investigational medicinal product code	Doxorubicin
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	160 - 210 mg/m2 milligram(s)/sq.meter
Investigational medicinal product name	Vepesid
Investigational medicinal product code	Etoposid
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	1050 - to 1950 mg/m2 milligram(s)/square meter
Investigational medicinal product name	Etopophos
Investigational medicinal product code	Etoposide phosphate
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	1207,5 - to 2242,5 mg/m2 milligram(s)/square meter
Investigational medicinal product name	Vincristin Bristol
Investigational medicinal product code	Vincristin
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	9 - to 15 mg/m2 milligram(s)/square meter
Investigational medicinal product name	Vinblastinsulfat-GRY
Investigational medicinal product code	Vinblastin
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	12 - to 24 UIntrmg/m2 milligram(s)/square meter
Investigational medicinal product name	Endoxan
Investigational medicinal product code	Cyclophosphamide
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	2500 - 5000 mg/m2 milligram(s)/square meter
Investigational medicinal product name	Uromitexan
Investigational medicinal product code	Mesna
Other name
Pharmaceutical forms	Solution for infusion
Routes of administration	Intravenous use
Dosage and administration details	3300 - to 6600 mg/m2 milligram(s)/square meter
Investigational medicinal product name	Prednison-ratiopharm
Investigational medicinal product code	Prednisone
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	2920 - to 4040 mg/m2 milligram(s)/square meter
Investigational medicinal product name	Granocyte
Investigational medicinal product code	Lenograstim
Other name
Pharmaceutical forms	Solution for injection
Routes of administration	Subcutaneous use
Dosage and administration details	40 - to 160 µg/m2 microgram(s)/square meter
Number of subjects in period 1 VECOPA Started 15 Completed 14 Not completed 1      Lack of efficacy 1

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	Overall trial
Reporting group description	-
Reporting group values Overall trial Total Number of subjects 15 15 Age categorical Units: Subjects     Children (2-11 years) 1 1     Adolescents (12-17 years) 14 14 Age continuous Units: years     median (full range (min-max)) 15.3 (8.2 to 17.8) - Gender categorical Units: Subjects     Male 15 15 Stage Units: Subjects     intermediate 4 4     advanced 11 11

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	VECOPA
Reporting group description	All patients received two induction cycles of OEPA (standard treatment). Patients with intermediate or advanced stage disease received one or two cycles of VECOPA (experimental). OEPA cycles consisted of vincristine 1.5 mg/m 2 intravenously (i.v.) on days 1, 8 and 15; etoposide 125 mg/m 2 i.v. on days 3 – 8; prednisone 60 mg/m 2 orally (p.o.) on days 1 – 15; and doxorubicin 40 mg/m 2 i.v. on days 1 and 15 VECOPA consisted of Etoposid 150 mg/m² i.v. days 1-3; Adriamycin 25mg/m²/i.v. day 21; Vinblastin 6 mg/m² i.v. days 1 and 21; Vincristin 1.5 mg/m2 i.v. days 8 and 29; Cyclophosphamide 1250 mg/m2 i.v. days 1 and 21;Prednisone 40 mg/m2 p.o. days 1-14 and 21-34

End points Top of page

Primary: Feasibility of VECOPA Top of page
End point title	Feasibility of VECOPA [1]
End point description	Rate of VECOPA cycles in which recovery of blood counts on day 21 and 42 was sufficient to allow continuation of therapy (i.e. leukocytes >= 1,8 x 10^9 /l and thrombocytes >= 50 x 10^9 /l and no active infection) We analysed cycles. 26 of 26 cycles were given in full dose. The primary endpoint required valid blood counts available for 21cycles.
End point type	Primary
End point timeframe	after end of VECOPA therapy
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This is a single arm trial. Reporting of statistical analyses in this database require at least two arms, otherwise an error message occurs.
End point values VECOPA Number of subjects analysed 14 [2] Units: cycles 16
Notes [2] - We report on 21 of 26 cycles (cycles with valid blood counts only).
No statistical analyses for this end point

Primary: Feasibility of VECOPA Top of page

Secondary: Event free survival (EFS) Top of page
End point title	Event free survival (EFS)
End point description	EFS was defi ned as the time from the start of treatment until the fi rst of the following events: progression/ relapse of disease, diagnosis of a secondary malignancy or death from any cause.
End point type	Secondary
End point timeframe	36 months after inclusion
End point values VECOPA Number of subjects analysed 14 Units: rate     number (confidence interval 95%) 0.857 (0.692 to 1)
No statistical analyses for this end point

Secondary: Event free survival (EFS) Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	From inclusion to up to 4 weeks after the last dose of chemotherapy
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	23.0
Reporting groups
Reporting group title	All patients
Reporting group description	-
Serious adverse events All patients Total subjects affected by serious adverse events      subjects affected / exposed 0 / 15 (0.00%)      number of deaths (all causes) 0      number of deaths resulting from adverse events 0
Frequency threshold for reporting non-serious adverse events: 0%
Non-serious adverse events All patients Total subjects affected by non serious adverse events      subjects affected / exposed 15 / 15 (100.00%) Investigations White blood cell count      subjects affected / exposed 15 / 15 (100.00%)      occurrences all number 65 Granulocyte count      subjects affected / exposed 15 / 15 (100.00%)      occurrences all number 54 Haemoglobin      subjects affected / exposed 14 / 15 (93.33%)      occurrences all number 45 Hepatic enzyme      subjects affected / exposed 14 / 15 (93.33%)      occurrences all number 35 Body temperature      subjects affected / exposed 8 / 15 (53.33%)      occurrences all number 10 Platelet count      subjects affected / exposed 5 / 15 (33.33%)      occurrences all number 9 Blood bilirubin      subjects affected / exposed 3 / 15 (20.00%)      occurrences all number 6 Blood creatinine      subjects affected / exposed 2 / 15 (13.33%)      occurrences all number 5 Pulmonary function test      subjects affected / exposed 2 / 15 (13.33%)      occurrences all number 5 Injury, poisoning and procedural complications Radiation associated pain      subjects affected / exposed 2 / 15 (13.33%)      occurrences all number 2 Nervous system disorders Motor dysfunction      subjects affected / exposed 4 / 15 (26.67%)      occurrences all number 10 Sensory disturbance      subjects affected / exposed 3 / 15 (20.00%)      occurrences all number 8 Headache      subjects affected / exposed 1 / 15 (6.67%)      occurrences all number 2 General disorders and administration site conditions Mucosal inflammation      subjects affected / exposed 11 / 15 (73.33%)      occurrences all number 21 Eye disorders Eye inflammation      subjects affected / exposed 3 / 15 (20.00%)      occurrences all number 3 Gastrointestinal disorders Vomiting      subjects affected / exposed 9 / 15 (60.00%)      occurrences all number 18 Constipation      subjects affected / exposed 8 / 15 (53.33%)      occurrences all number 13 Diarrhoea      subjects affected / exposed 8 / 15 (53.33%)      occurrences all number 9 Dysphagia      subjects affected / exposed 7 / 15 (46.67%)      occurrences all number 8 Dyspepsia      subjects affected / exposed 1 / 15 (6.67%)      occurrences all number 2 Salivary gland disorder      subjects affected / exposed 1 / 15 (6.67%)      occurrences all number 1 Skin and subcutaneous tissue disorders Skin disorder      subjects affected / exposed 2 / 15 (13.33%)      occurrences all number 3 Musculoskeletal and connective tissue disorders Back pain      subjects affected / exposed 1 / 15 (6.67%)      occurrences all number 2 Infections and infestations Infection      subjects affected / exposed 8 / 15 (53.33%)      occurrences all number 12 Herpes labialis      subjects affected / exposed 1 / 15 (6.67%)      occurrences all number 2

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported
Online references
http://www.ncbi.nlm.nih.gov/pubmed/25204374

More information Top of page