An international collaborative study to discontinue Imatinib/Glivec® in pediatric CML patients with sustained complete molecular response

Chronic myeloid leukemia is a rare disease in children; SEER databases record
an incidence of 2% of all leukemias in children < 15 years (accounting for 1
case/million/year) increasing up to 9% in children aged 15-19 years (2.2
cases/million/year).
Presently treatment consists of BCR/ABL kinase inhibitors as first choice
drugs, in both adults and children. Only approximately 60% of the treated
children have a sibling donor or a good matched non-related donor for stem cell
transplantation. All others remain on BCR/ABL kinase inhibitor such as imatinib
and/or newer generations of BCR/ABL targeting kinase inhibitors.
Recently, several adverse long-term effects have been described in adult series
and scarce case reports in children treated with BCR/ABL kinase inhibitors,
such as imatinib. For instance, decreased growth development, aberrant bone
composition and incomplete pubertal development are reported as a result of
long-term treatment with tyrosine kinase inhibitors such as Imatinib. Due to
the rareness of the disease in children, collaborating international pediatric
studies are lacking.
Besides opening an international CML registry to investigate the long-term
(side-) effects, the possibility of imatinib discontinuation needs to be
explored as a possible final solution for the disease and long-term side
effects. Many adolescents already discontinue Imatinib themselves. In the
meantime, promising results are described in small series of adult CML patients
in which imatinib is stopped; 40% remained in a complete molecular response.
Most patients (>90%) with molecular relapse experienced this relapse early (<7
months) after stopping Imatinib. All relapsed patients achieved a second
molecular remission after restarting Imatinib. So, the international CML
treating physicians of the IBFM are confronted with drug discontinuation of
several patients themselves, or with reasons such as impaired growth
development and/or complications or toxicity.

Therefore, this international collaborative study will determine the efficacy
of discontinuation of Imatinib on sustained complete molecular response in
Philadelphia chromosome positive CML pediatric patients treated with imatinib.

To estimate the percentage of quantitative RT-PCR negative pediatric CML
patients in which Imatinib discontinuation result in sustained complete
molecular remission
To determine whether restarting of Imatinib in case of molecular relapse
results in a molecular remission again.

Investigate rates of relapses, and duration of complete molecular response
after discontinuation of Imatinib, survival and progression and efficacy of
restarting Imatinib after molecular relapse.

'Discontinuation of Imatinib at complete molecular response.

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