Clinical Trial Results:
Evaluation of anthroposophic supportive medicine on treatment-related toxicity in children receiving cancer therapy
Summary
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EudraCT number |
2004-002711-83 |
Trial protocol |
DE |
Global end of trial date |
23 Mar 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Apr 2022
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First version publication date |
25 Apr 2022
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Other versions |
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Summary report(s) |
CSR Summary of Results |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
09-2004 PaedonkoChar
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Additional study identifiers
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ISRCTN number |
ISRCTN64676790 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Helixor Heilmittel GmbH
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Sponsor organisation address |
Fischermühle 1, Rosenfeld, Germany, 72348
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Public contact |
Sabine Rieger, Helixor Heilmittel GmbH, +49 7428 / 935 850, srieger@helixor.de
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Scientific contact |
Dr. rer. nat. Michael Schink, Helixor Heilmittel GmbH, +49 7428 / 935 860, mschink@helixor.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
21 Mar 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Mar 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
influence of an anthroposophic supportive therapy concept on the chemotherapy-associated toxicity was investigated by means of a toxicity sumscore consisting of the NCI-CTC-scales hematology, mucositis, general condition and the GPOH-modified scale for infection
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Protection of trial subjects |
- the study was conducted in accordance with all relevant laws and regulations relating to clinical studies and the protection of patients
- the investigator ensured pseudonymity of the patients, signed patient informed consent and patient enrolment log were kept striktly confidential to enable patient identification at the site
- minimisation of pain of subcutaneous injection by use of INJEX needle free injector (optional)
- further measures were not necessary
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Background therapy |
participants of all groups received standard chemotherapy according to individual tumor type and stage | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
24 Nov 2005
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 340
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Worldwide total number of subjects |
340
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EEA total number of subjects |
340
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
22
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Children (2-11 years) |
205
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Adolescents (12-17 years) |
113
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Recruitment period from 11/2005 until 11/2013 in 12 trial sites in Germany Patients were assigned to the verum or control group by stratified randomization according to tumor entities and chemotherapy protocols. | |||||||||||||||
Pre-assignment
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Screening details |
Fulfilment of inclusion and non-fulfilment of exclusion criteria. No further screening criteria defined. Latest possible date of randomisation was the 10th day after start of chemotherapy protocol. In total, 556 patients were screened. | |||||||||||||||
Period 1
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Period 1 title |
treatment period
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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control group | |||||||||||||||
Arm description |
standard therapy: chemotherapy according to underlying disease with standardised concomitant treatments | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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verum group | |||||||||||||||
Arm description |
anthroposophic supportive therapy in addition to standard therapy (chemotherapy according to underlying disease with standardised concomitant treatments) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Helixor A
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Investigational medicinal product code |
L01CH01
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subcutaneous injections 2 times a week
stepwise dose increase starting with 1 mg until occurence of local or systemic reaction to investigational drug
maximum allowed dose: 100 mg
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Investigational medicinal product name |
Cichorium e planta tota 5% Globuli velati
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 3x5 globules per day
dose for children ≥ 4 years: 3x7 globules per day
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Investigational medicinal product name |
Oxalis Folium Rh D4 aqueous dilution
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral drops, solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 3x5 drops per day
dose for children ≥ 4 years: 3x7 drops per day
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Investigational medicinal product name |
Phosphorus D8 Globuli velati
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 5 globules (in the morning)
dose for children ≥ 4 years: 10 globules (in the morning)
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Investigational medicinal product name |
Phosphorus D30 Globuli velati
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 5 globules (in the evening)
dose for children ≥ 4 years: 10 globules (in the evening)
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Investigational medicinal product name |
Aurum/Prunus liquid dilution for injection
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1 ampoule as an intravenous infusion before each chemotherapy
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Investigational medicinal product name |
Aurum Valeriana Globuli velati
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 5 globules up to every 2 hours (except at night)
dose for children ≥ 4 years: 10 globules up to every 2 hours (except at night)
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Investigational medicinal product name |
Bryophyllum 5% solution for injection
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
In the recovery phase after sedation, anesthesia or punctures:
dose for children < 4 years: 5 ml as an intravenous infusion
dose for children ≥ 4 years: 10 ml as an intravenous infusion
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Investigational medicinal product name |
Bryophyllum 50%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral powder
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Routes of administration |
Oral use
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Dosage and administration details |
For psychological and somatic side effects or at the end of steroid administration: 1 teaspoon 3 times a day;
for sleep disorders daily:
dose for children < 4 years: 1/2 teaspoon 3 times a day
dose for children ≥ 4 years: 1 teaspoon 3 times a day
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Investigational medicinal product name |
Calendula (mother tincture)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral drops, solution
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 5 drops 3 times a day
Dose for children ≥ 4 years: 10 drops 3 times a day
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Investigational medicinal product name |
Nux vomica D4 liquid dilution for injection
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1 ampoule as an intravenous infusion before each chemotherapy
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Investigational medicinal product name |
Nux vomica e semine D4 Globuli velati
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 3 globules daily to hourly
dose for children ≥ 4 years: 5 globules daily to hourly
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Investigational medicinal product name |
Oxalis ointment 30%
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Ointment
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Routes of administration |
Topical use
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Dosage and administration details |
if necessary or regularly moist warm wrap at noon
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Investigational medicinal product name |
Ratanhia comp.
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Mouthwash
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Routes of administration |
Oral use
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Dosage and administration details |
To be used only as a dilution (30 drops per 100 ml of water) Besides this mouthwash, no other conventional is allowed
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Investigational medicinal product name |
Solum Oil
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pharmaceutical dose form not applicable
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Routes of administration |
Topical use
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Dosage and administration details |
Rubbing of individual body parts (for example extremities / back); if necessary, ideally in the evening
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Investigational medicinal product name |
Meteoreisen Globuli velati
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 3x5 globules per day
dose for children ≥ 4 years: 3x10 globules per day
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Investigational medicinal product name |
Argentum metallicum praeparatum D30 (liquid dilution for injection)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Dose for children < 4 years: 1 ampoule as an intravenous infusion once a day before intravenous antibiotic administration
dose for children ≥ 4 years: 2 ampoules as an intravenous infusion once a day before intravenous antibiotic administration
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Investigational medicinal product name |
Gentiana Magen Globuli velati
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 3x5 globules per day
dose for children ≥ 4 years: 3x10 globules per day
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Investigational medicinal product name |
Lachesis D8 Dilution
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pillules
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Routes of administration |
Oral use
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Dosage and administration details |
Dose for children < 4 years: 3x5 drops per day (to be diluted)
dose for children ≥ 4 years: 3x7 drops per day (to be diluted)
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Period 2
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Period 2 title |
follow-up period
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Is this the baseline period? |
No | |||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Follow-up control group | |||||||||||||||
Arm description |
Patients who have finished at least the first observation period of chemotherapy were observed up to five years no limitations for treatment during follow-up period after conclusion of standard therapy | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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Follow-up verum group | |||||||||||||||
Arm description |
Patients, who have finished at least the first observation period of chemotherapy and have received basic remedies at least during this period, were observed up to five years no limitations for treatment during follow-up period after conclusion of standard therapy | |||||||||||||||
Arm type |
No intervention | |||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
control group
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Reporting group description |
standard therapy: chemotherapy according to underlying disease with standardised concomitant treatments | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
verum group
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Reporting group description |
anthroposophic supportive therapy in addition to standard therapy (chemotherapy according to underlying disease with standardised concomitant treatments) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
control group
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Reporting group description |
standard therapy: chemotherapy according to underlying disease with standardised concomitant treatments | ||
Reporting group title |
verum group
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Reporting group description |
anthroposophic supportive therapy in addition to standard therapy (chemotherapy according to underlying disease with standardised concomitant treatments) | ||
Reporting group title |
Follow-up control group
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Reporting group description |
Patients who have finished at least the first observation period of chemotherapy were observed up to five years no limitations for treatment during follow-up period after conclusion of standard therapy | ||
Reporting group title |
Follow-up verum group
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Reporting group description |
Patients, who have finished at least the first observation period of chemotherapy and have received basic remedies at least during this period, were observed up to five years no limitations for treatment during follow-up period after conclusion of standard therapy | ||
Subject analysis set title |
control group ITT subset
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
This ITT population includes all patients enrolled in the study who have been randomised, regardless of protocol violations in the course of the study
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Subject analysis set title |
verum group ITT subset
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
This ITT population includes all patients enrolled in the study who have been randomised and who have received basic medications at least during one complete observation period, regardless of protocol violations in the course of the study.
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Subject analysis set title |
Follow-up control group EFS
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
This modified ITT-population includes all patients enrolled in the study and randomised into the control group
• with complete remission (CR) at the end of the intensive phase of chemotherapy (main study)
• for which a follow-up documentation sheet is available 5 years after diagnosis. This documentation sheet must contain an indication (yes or no) on relapse, death and second malignancy
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Subject analysis set title |
Follow-up verum group EFS
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
This modified ITT-population includes all patients enrolled in the study and randomised into the verum group
• with complete remission (CR) at the end of the intensive phase of chemotherapy (main study)
• for which a follow-up documentation sheet is available 5 years after diagnosis. This documentation sheet must contain an indication (yes or no) on relapse, death and second malignancy
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Subject analysis set title |
Follow-up control group OS
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
This modified ITT-population includes all patients enrolled in the study and randomised into the control group for whom a follow-up documentation form has been completed 5 years after diagnosis
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Subject analysis set title |
Follow-up verum group OS
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
This modified ITT-population includes all patients enrolled in the study and randomised into the verum group for whom a follow-up documentation form has been completed 5 years after diagnosis
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Subject analysis set title |
control group PP subset
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP population includes all patients enrolled in the study who have been randomised and have gone through all chemotherapy units until conclusion of last chemotherapy unit without occurrence of serious protocol violations.
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Subject analysis set title |
verum group PP subset
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The PP population includes all patients enrolled in the study who have been randomised and have gone through all chemotherapy units until conclusion of last chemotherapy unit without occurrence of serious protocol violations. Additionally at least 75% of basic remedies of study medication have been administered.
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End point title |
Reduction of toxicity sum score of selected NCI-CTC-scales | ||||||||||||||||||||
End point description |
influence of an anthroposophic supportive therapy concept on the chemotherapy-associated toxicity was investigated by means of a toxicity sumscore consisting of the NCI-CTC-scales hematology, mucositis, general condition and the GPOH-modified scale for infection
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End point type |
Primary
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End point timeframe |
Depending on the chosen chemotherapy schedule time frame lasted from beginning of first chemotherapy treatment unit until 28 days after termination of last chemotherapy treatment unit.
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Statistical analysis title |
Comparison of toxicity sum score ITT group | ||||||||||||||||||||
Comparison groups |
control group ITT subset v verum group ITT subset
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Number of subjects included in analysis |
279
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.257 | ||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||
Confidence interval |
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Statistical analysis title |
Comparison of toxicity sum score PP group | ||||||||||||||||||||
Comparison groups |
control group PP subset v verum group PP subset
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Number of subjects included in analysis |
208
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Analysis specification |
Post-hoc
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Analysis type |
superiority | ||||||||||||||||||||
P-value |
= 0.716 | ||||||||||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||||||||||
Confidence interval |
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End point title |
ALL-Non-HR; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
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End point type |
Secondary
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End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
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Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
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Number of subjects included in analysis |
101
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Analysis specification |
Post-hoc
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.185 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
ALL-HR; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
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End point type |
Secondary
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End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
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Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
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Number of subjects included in analysis |
8
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Analysis specification |
Post-hoc
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.439 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
COALL-HR; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
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End point type |
Secondary
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End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
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Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.756 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
ALL-Rez; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
12
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.992 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
AML; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
17
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.229 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
B-NHL; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
16
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.063 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Rhabdomyosarcoma; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
5
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.221 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Osteosarcoma; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
7
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.728 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Morbus Hodgkin; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
28
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.407 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Ewing-Sarcoma; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
21
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.441 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Medulloblastoma/Ependymoma; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
4
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.182 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Neuroblastoma; overall survival | ||||||||||||
End point description |
Overall survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of death or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparison of overall survival | ||||||||||||
Comparison groups |
Follow-up control group OS v Follow-up verum group OS
|
||||||||||||
Number of subjects included in analysis |
14
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.025 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
ALL-Non-HR; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
93
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.686 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
ALL-HR; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
8
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.436 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
COALL-Non-HR; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
18
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.967 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
COALL-HR; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
13
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.331 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
ALL-Rez; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
7
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.919 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
AML; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
12
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.306 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
B-NHL; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
13
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.28 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Rhabdomyosarcoma; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
3
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.157 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Morbus Hodgkin; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
15
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.802 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Ewing-Sarcoma; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
14
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.897 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Medulloblastoma/Ependymoma; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up verum group EFS v Follow-up control group EFS
|
||||||||||||
Number of subjects included in analysis |
4
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.182 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||
End point title |
Neuroblastoma; event-free survival | ||||||||||||
End point description |
Event-free survival within a period of 5 years
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Date of initial diagnosis until date of event (relapse, death or second malignancy) or end of 5-years observation period
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Comparion of event free survival | ||||||||||||
Comparison groups |
Follow-up control group EFS v Follow-up verum group EFS
|
||||||||||||
Number of subjects included in analysis |
4
|
||||||||||||
Analysis specification |
Post-hoc
|
||||||||||||
Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.083 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
continuous reporting of adverse events by investigator via remote data entry, assessment of reports yearly within framework of annual safety reports (serious adverse reactions assessed quarterly)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
safety population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The safety population included all patients recruited into the study who were randomized and who received the basic medication at least once during the course of the study and/or on-demand remedies of the investigational medication. For this population adverse events (AE) and serious adverse events (SAEs) were assessed. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
28 Aug 2006 |
Essential changes were:
- Updates, specifications and correction of chemotherapy protocols
- Frequency of administration of an IV product
- Addition of an investigation of mistletoe lectin-antibodies for a sample of n = 15 patients of verum group in order to get information about the application of Helixor® A
- Specification for the early withdrawal of a patient from the study
- Correction of expected end of study
- Complete revision of the chapter on definition, recording and evaluation of adverse events |
||
01 Sep 2008 |
Essential changes were:
- Inclusion of new trial sites
- Prolongation of recruitment time due to slow recruitment
- Update of existing an new CT protocols
- Specification of an exclusion criterion
- Specification and supplementation of the analysis population
- Supplement of side effects
- Elimination of an additional analysis due to unsuitability |
||
18 Jan 2010 |
Essential changes were:
- Downsizing of the DSMC to exclude people directly involved in the study
- Update and corrections of the CT protocols
- Prolongation of recruitment time and study duration
- Recruitment of further trial sites
- Side effects: Adaption to SPC
- Update of PIL and SPC
- Supplement for control group regarding procedure after the end of the study
- Specification of definition for follow up
- Elimination of redundantinformation, statistical analysis: specification of analysis
- Clear description for the documentation in case of early withdrawal of a patient
|
||
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. | |||
The secondary endpoint Event-free Survival (EFS) could not be analysed for some subgroups due to too small analytical populations for valid comparison of verum vs control population |