E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Therapy for childhood Hodgkin’s lymphoma shall be further optimised to avoid over-treatment and decrease long-term complications. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. Are 5 year event free survival (EFS) rate estimates in patients with adequate response after 2 OEPA treated without radiotherapy consistent with a target EFS rate of 90% in all treatment groups? 2. Can Procarbazine be safely replaced by Dacarbazine in therapy groups TG-2 and TG-3 without a deterioration of EFS (randomised comparison of COPDAC and COPP)? 3. Description of treatment outcome to a standardised risk adapted relapse strategy |
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E.2.2 | Secondary objectives of the trial |
1. Is the 5 year event free survival (EFS) rate in patients with inadequate response after 2 OEPA who receive standard involved field radiotherapy consistent with a target EFS rate of 90% estimates in all treatment groups? 2. Does substitution of Dacarbazine for Procarbazine in TG-2 and -3 patients decrease the rate of infertility in males and premature menopause for females? |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• diagnosis of classic Hodgkin’s lymphoma • patient aged under 18 years at time of diagnosis • written informed consent of the patient and/or the patient’s parents or guardian according to national laws |
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E.4 | Principal exclusion criteria |
pre-treatment of Hodgkin’s lymphoma differing from study protocol (except recommended pre-phase therapy of a large mediastinal tumour) • known hypersensitivity or contraindication to study drugs • diagnosis of lymphocyte predominant Hodgkin’s lymphoma • prior chemotherapy or radiotherapy |
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E.5 End points |
E.5.1 | Primary end point(s) |
Event free survival (EFS) defined as time from registration until the first of the following events: • progression/relapse of disease • diagnosis of a secondary malignancy • death of any cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
5-year EFS rates for TG-1 and TG-2 & -3 will be estimated (with 95% confidence intervals) in patients with adequate response after 2 OEPA (and secondarily also in patients with inadequate response). |
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E.5.2 | Secondary end point(s) |
1. Overall survival (OS) 2. Progression free survival (PFS) 3. CTC (Common toxicity criteria) toxicity levels of therapy elements 4. Evidence of male infertility score / Female sexual functioning score 5. Long-term consequences (premature menopauses), secondary cancer etc.) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 5 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Starting after the second year of recruitment annual intermediate analyses are intended if at least 80 randomised patients have a median observation time of at least 18 months. A proportional hazard model with the factors treatment group (TG-2 versus TG-3), SRA stratum and therapy (COPP versus COPDAC) is fitted. According to data of the pilot study with COPDAC dramatic differences are not to be expected. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |