E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early stage nodular lymphocyte predominant Hodgkin's lymphoma [nLPHL] |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029602 |
E.1.2 | Term | Non-Hodgkin's lymphoma stage I |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Currently more than 95% of children with early stage nodular Lymphocyte Predominant Hodgkin's lymphoma [nLPHL] will be cured.The majority of children in Europe and the USA will receive treatment which includes both toxic chemotherapy and radiotherapy. The principal research questions of this trial are: Can chemotherapy and radiotherapy be completely avoided in children who have had all of their diseased lymph nodes removed completely by straightforward uncomplicated surgery? If surgical removal of the involved lymph nodes is considered difficult or unsuccessful, then can short course of low intensive chemotherapy be curative? |
|
E.2.2 | Secondary objectives of the trial |
Thirdly, if the disease recurs in patients who have only had surgical removal of the diseased lymph nodes as their primary treatment, can this group of patients be cured with subsequent chemotherapy? Finally, we are also aiming to describe the clinical outcome to the recommended relapsed treatment strategy of those patients who relapse after low intensity chemotherapy [less than 10-15%] |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: • Nodular lymphocyte-predominant Hodgkin’s lymphoma confirmed by reference pathology. • Initial stage IA/IIA (according to local staging) or relapse stage IA or IIA and residual tumour after relapse biopsy and no additional surgery planned in nLP patients relapsing after surgery alone • 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 In certain European countries very young patients may have to be excluded in order to comply with national laws or formal insurance requirements.
|
|
E.4 | Principal exclusion criteria |
Exclusion criteria: • Pre-treatment of Hodgkin’s lymphoma differing from study protocol • Any extra-nodal involvement • Inability to fulfil protocol requirements for imaging (CT, MRI, FDG-PET) at staging and response assessment • Known hypersensitivity or contraindication to study drugs • Prior chemotherapy or radiotherapy • Current or recent therapy (within 30 days prior to the start of trial treatment) with steroids • Current or recent (within 30 days prior to the start of trial treatment) treatment with another investigational drug or participation in another investigational trial • Other (simultaneous) malignancies • Severe concomitant diseases (e.g. immune deficiency syndrome) • Known HIV positivity • Pregnancy and / or lactation • Females who are sexually active refusing to use effective contraception (oral contraception, intrauterine devices, barrier method of contraception in conjunction with spermicidal jelly or surgical sterile) (except for surgery only.
Subsequent exclusion criteria: Patients are excluded from the study after registration if: • Documents or material ascertained before study inclusion show that an exclusion criterion was fulfilled or an inclusion criterion was not met • The patient and/or the patient’s parents or guardian withdraw(s) his/her/their consent to further study participation.
If central review results in upstaging above stage IA/IIA the patient is still documented in the scope of the study but not eligible for treatment in the study. The patient’s physician then decides together with the patient/parents or guardian as to the most appropriate therapy. The study chairpersons decide on the exclusion along with the biometrician of the study. Subsequent exclusion of a patient can be requested by a trial site only in writing. Subsequent exclusion of a patient differs from an individual therapy withdrawal. In the latter case the treatment of the patient according to protocol is terminated, but follow-up and documentation (data collection in the CRF) is continued according to protocol and the patient appears in all relevant analyses.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. 5 year Event Free Survival rates for Surgery alone group 2. 5 year Event Free Survival rates for CVP group
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Event free survival (EFS):= time from registration until the first of the following events: • additional treatment for Hodgkin’s Lymphoma • progression/relapse of disease • occurrence of a secondary malignancy • death by any cause For patients allocated to the CVP group failure to achieve a good response constitutes an indication for additional treatment and counts as event. |
|
E.5.2 | Secondary end point(s) |
1.Overall survival in both groups of patients 2.Upstaging at relapse [i.e. stage > IIA, B symptoms, extra-nodal disease] 3.Transformation rate to diffuse B cell NHL 4.Death from any cause
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each such event has to be reported immediately and commented in detail. If 5 alarming events occur in one of the study populations the opinion of the DMC has to be requested. In addition relapses will be monitored: As the relapses will occur within the first five years a formal monitoring with immature data is difficult without assuming a certain form of the underlying hazard function. The analysis will be performed annually, but only if at least 30 patients have a follow-up of more than 12 months past the end of therapy in the respective group. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 22 |
E.8.5 | The trial involves multiple Member States | No |
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
|
This trial is an event driven trial therefore the end of trial would be when the endpoint has been reached. It is estimated it will be 5 years after the last trial treatment of any patient. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |