International cooperative prospective study for children and adolescents with standard risk ALK-positive anaplastic large cell lymphoma (ALCL) estimating the efficacy of Vinblastine.

The development of standard multi-agent chemotherapy has reached its limits for
the treatment of ALK-positive ALCL: intensification did not increase survival
but the risk of late effects. In ALCL patients a 5-year EFS rate of 70% is
achieved independently of the chemotherapy regimen. Vinblastine monotherapy
reaches more than 80% remission-rates and long-term survival in relapsed
patients. The experiences with Vinblastine in relapse therapy suggest that a
low-dose long-term therapy could be as effective as standard short-term
multi-agent therapy.

Patients who can be cured by Vinblastine are spared both acute and late
toxicity of the multi-agent chemotherapy including Etoposide, alkylators and
anthracyclines. Further advantages for single drug Vinblastine therapy are that
patients can be treated as outpatients. They can go to school / work and have
no major restrictions in daily live in contrast to standard intensive
multi-agent chemotherapy. A distinct disadvantage is the duration of treatment
and the associated frequent outpatient visits and vinblastine administration.

Since safety is not an issue with Vinblastine monotherapy, its efficacy in
relapsed patients has been shown, and overall survival is foreseeable not
reduced by Vinblastine, this study forms the basis towards establishing a low
toxicity new chemotherapy backbone substituting multi-agent chemotherapy. This
would provide a new basis to study the addition of targeted therapies like
ALK-inhibitors.

This study has been transitioned to CTIS with ID 2022-501454-11-00 check the CTIS register for the current data.

PRIMARY OBJECTIVE:
- To show that it is possible to cure at least 75% of patients belonging to the
SR group with Vinblastine-monotherapy for 24 months.

SECONDARY OBJECTIVE:
- To describe overall survival and treatment related mortality of 24 months
Vinblastine monotherapy.
- To identify clinical, pathological and biological factors predictive of
progressive disease during / after VBL therapy.
- 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 (between day 17-22), 3 months and 6
months of treatment (including a possible pre-phase) assessed by appropriate
imaging methods

ALCL-VBL is a collaborative multi-centre, open-label non-randomized study of
international groups with the intention of optimizing the treatment results in
children and adolescents with standard risk ALK-positive ALCL by assessing the
efficacy of a 24-months Vinblastine monotherapy after a screening phase for
stratification.

Vinblastine monotherapy: 6 mg/m2 (max 10 mg) intravenous (i.v.) for a total
treatment duration of 24 months, weekly for 18 months and bi-weekly for the
final 6 months

Although the treatment within this protocol takes longer than the current
standard therapy, it is anticipated that the toxicity and burden are lower.
Patients who can be cured by Vinblastine are spared both acute and late
toxicity of the standard multi-agent chemotherapy including Etoposide,
alkylators and anthracyclines. During the treatment they can go to school /
work and have no major restrictions in daily live in contrast to standard
intensive multi-agent chemotherapy.

All diagnostic assessments are comparable to the standard of care assessments.
When participants consent to add-on studies, we will draw extra blood (max. 15x
10 ml) and ask them to complete Quality of Life questionnaires (5 timepoints).