E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pediatric oncology, acute lymphoblastic leukemia, nephroblastoma, medulloblastoma, low-grade glioma, Hodgkin lymphoma, rhabdomyosarcoma |
Kinderoncologie, acute lymfatische leukemie, nefroblastoom, medulloblastoom, laaggradig glioom, Hodgkin lymfoom en rhabdomyosarcoom |
|
E.1.1.1 | Medical condition in easily understood language |
Childhood cancer |
Kinderkanker |
|
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 | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001690 |
E.1.2 | Term | ALL |
E.1.2 | System Organ Class | 100000004864 |
|
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 |
To evaluate whether the administration of vincristine (VCR) in children with acute lymphoblastic leukemia, nephroblastoma, medulloblastoma, low-grade glioma, Hodgkin lymphoma or rhabdomyosarcoma by one-hour infusions leads to less peripheral neuropathy (PNP) compared to the administration by short-term (1-5 minutes) infusions or injections. |
Deze studie heeft tot doel te onderzoeken of de toediening van vincristine (VCR) bij kinderen met ALL door middel van één-uurs-infusen acute lymfatische leukemie, nefroblastoom, medulloblastoom, laaggradig glioom, Hodgkin lymfoom en rhabdomyosarcoom leidt tot minder PNP dan toediening door middel van kortdurende infusies |
|
E.2.2 | Secondary objectives of the trial |
• evaluate if the administration of VCR in children with cancer by one-hour infusions leads to better self-reported quality of life compared to the administration by short-term infusions. • evaluate if the administration of VCR in children with cancer by one-hour infusions leads to less direct and indirect medical costs compared to the administration by short-term infusions. • To evaluate if the administration of VCR in children with cancer by one-hour infusions leads to equal or better treatment efficacy compared to the administration by short-term infusions. • To compare the pharmacokinetic parameters of patients receiving both administration methods and to relate these parameters to the degree of PNP. • To validate/confirm the relationship between SNPs known to be associated with VCR-induced PNP (through influencing pharmacokinetics of VCR or through genetically increased susceptibility) and the degree of PNP of patients receiving both administration methods. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• age between 2 and 19 years. • treated for cancer according to a treatment protocol which includes at least 6 administrations of VCR of which 4 are administered within a maximum period of 6 weeks; • diagnosed with a cancer diagnosis of which the Iincidence in the Netherlands is of more than 5 diagnosed patients per year • written informed consent
|
|
E.4 | Principal exclusion criteria |
• patient or parent refusal • history of PNP or other pre-existing neurologic conditions before ALL diagnosis; • pre-existing severe mental retardation; • having parents/ guardians who are unable to communicate in the Dutch language.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome of the study is peripheral neuropathy (PNP). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
PNP will be evaluated at several points in time: 3-7 measurements in total |
|
E.5.2 | Secondary end point(s) |
Secondary parameters include quality of life, (in)direct medical costs, therapeutic effectiveness, and pharmacokinetic and genetic outcomes. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Quality of life and pharmacokinetic measures: 1-5 times during VCR-therapy, 1 time at the end of therapy, 1 time at 6 months after the end of VCR-therapy. Medical costs: 0-1 times duiring therapy and 0-1 time post-therapy. Therapeutic effectiveness: thorough monitoring during the study e.g by evaluating residual disease (MRD), or imaging techniques, cumulative incidence of relapses, event-free survival (EFS) and overall survival (OS). These data concern readily available data which will be provided by the DCOG. Genetics: exome sequencing at one time point. |
|
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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | Yes |
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 | Yes |
E.8.2.3.1 | Comparator description |
Vincristine administered by bolus injections/infusions |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
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 | No |
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
|
The end of the study is defined as the last patient’s last visit. In case the study is ended prematurely, the sponsor will notify the accredited METC and the competent authority within 15 days, including the reasons for the premature termination. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |