E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
standard risk ALK-positive anaplastic large cell lymphoma (ALCL) |
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E.1.1.1 | Medical condition in easily understood language |
anaplastic large cell lymphoma (ALCL) |
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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 |
The primary objective of the study is to show that it is possible to cure at least 75% of patients belonging to the SR group with Vinblastine monotherapy for 24 months. Endpoint is the probability of event-free-survival (pEFS) at 3 years, with event-free-survival (EFS) defined as the time of diagnosis to the first event (progressive disease, nonresponse, secondary malignancy or death due to any cause) or last follow-up.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives and endpoints of the study are •To describe overall survival and treatment related mortality of 24 months Vinblastine monotherapy. Overall survival is the time from diagnosis to death of any cause or last follow-up. •To identify clinical, pathological and biological factors predictive of progressive disease during / after VBL therapy. The time of progressive disease is the time from diagnosis to progressive disease or a competing event (death from any cause, secondary malignancy) or last follow-up. •To estimate the rate of SR patients requiring multi-agent chemotherapy •To describe the toxicity of Vinblastine given for 24 months rated with CTCAE v4.03. •To describe the response after 3 weeks (on day 17-22), 3 months and 6 months of treatment (including a possible pre-phase) assessed by appropriate imaging methods
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Stratification into the standard risk group (SR) by screening: o Newly diagnosed ALK-positive ALCL o Stage I not completely resected, or stage II or stage III o MDD negative • Age < 18 years • Informed consent of the parents/legal guardians (and assent of the competent child) for study participation and data collection, storage and handling given before study entry • Participation in national / study group's reference pathology • Follow-up for at least 3 years after enrolment is expected • Application of a highly effective contraceptive method (Pearl index <1) in sexually active patients |
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E.4 | Principal exclusion criteria |
• Progressive disease during a possible clinically indicated pre-phase treatment before inclusion in the study • Steroids for more than 2 days or chemotherapy pre-treatment before taking the screening sample for MDD • Chemotherapy pre-treatment before start of the study treatment except for o the obligatory initial intrathecal triple therapy with Methotrexate, Cytarabine and Prednisolone (or Hydrocortisone respectively) o a possible clinically indicated pre-phase including up to 5 days of steroids combined with up to 3 doses of Vinblastine (and up to 2 doses of Cyclophosphamide) • Pregnancy or lactation period • Contraindications for the treatment with Vinblastine: o hypersensitivity against VBL or other vinca-alkaloids o leukopenia, other than in the context of the ALCL o severe uncontrolled infection • Other medical, psychiatric, familial or social condition prohibiting treatment according to the protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Endpoint is the probability of event-free-survival (pEFS) at 3 years, with event-free-survival (EFS) defined as the time of diagnosis to the first event (progressive disease, nonresponse, secondary malignancy or death due to any cause) or last follow-up. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary objectives and endpoints of the study are •To describe overall survival and treatment related mortality of 24 months Vinblastine monotherapy. Overall survival is the time from diagnosis to death of any cause or last follow-up. •To identify clinical, pathological and biological factors predictive of progressive disease during / after VBL therapy. The time of progressive disease is the time from diagnosis to progressive disease or a competing event (death from any cause, secondary malignancy) or last follow-up. •To estimate the rate of SR patients requiring multi-agent chemotherapy •To describe the toxicity of Vinblastine given for 24 months rated with CTCAE v4.03. •To describe the response after 3 weeks (on day 17-22), 3 months and 6 months of treatment (including a possible pre-phase) assessed by appropriate imaging methods |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 years post treatment or last follow up visit |
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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 | 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) | 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 | 50 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Japan |
Austria |
Belgium |
Denmark |
Finland |
France |
Germany |
Hungary |
Iceland |
Netherlands |
Norway |
Poland |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
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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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One year after end of treatment of the last recruited patient |
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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 | 8 |
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 | 8 |
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 |