VINILO-arm: Vinblastine and nilotinib given in combination at the RD defined in the Phase I part:
Vinblastine: administered in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle.
Nilotinib (Tasigna®): orally BID given continuously on Days 1- 28 Recommended doses of the drug combination will be reconsidered at an interim stage of the phase II trial after the analysis of the delayed toxicity encountered in the first 20 patients treated at the initial RD (adaptive design).

Control Vinblastine only arm:
· Vinblastine 6 mg/m2 given in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle.
Each 28-day cycle is repeated on Day 29/Day 1.
In both treatment groups, dose reductions and/or administration delays will be performed in case of severe hematological and/or non hematological toxicities while on treatment.
Vinblastine will be temporarily stopped in case of neutropenia <1 x109/L or thrombopenia <75 x 109/L. It could be re-started at a reduced dose after complete recovery.
Patients benefiting from study treatment may continue up to 12 cycles as long as the toxicity-benefit ratio is adequate.

Refractory Low-grade Gliomas

Recurrent Low-grade Gliomas

Vinblastine: administered in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle.
Nilotinib (Tasigna®): orally BID given continuously on Days 1- 28

Vinblastine + Nilotinib

· Vinblastine 6 mg/m2 given in a 15-minute infusion, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle.

Vinblastine

Medical University of Vienna

Rigshospitalet

Gustave Roussy

Koordinierungszentrum für Klinische Studien (KKS) der Charité

University Hospital of Padua

Erasmus MC/Sophia Children's Hospital

Fundació Sant Joan de Déu

Swiss Pediatric Oncology Group

Cancer Research UK Clinical Trials Unit School of Cancer Sciences University of Birmingham

Study of Vinblastine in Combination With Nilotinib in Children, Adolescents, and Young Adults

Phase I-II Study of Vinblastine in Combination With Nilotinib in Children, Adolescents, and Young Adults With Refractory or Recurrent Low-Grade Glioma

PFS computed as the time interval between the date of study entry and the date of tumor progression or death (whatever the cause of death). The progression will be defined either radiologically (>25% increase in two-dimension measurements or appearance of new lesions compared to the baseline or to the best response after initiation of therapy) or clinically by new symptoms related to tumor progression (significant decrease of visual acuity, new or worsening neurological deficit). Hydrocephaly is not considered as progression per se.

Gustave Roussy, Cancer Campus, Grand Paris

Innovative Therapies For Children with Cancer Consortium

Nilotinib (Tasigna®): 115 to 350 mg/m2 twice daily (BID) orally given continuously (115 mg/m2 once daily if de-escalation requested
Vinblastine: 3 to 6 mg/m2 once weekly in a 15-minute infusion, on Days 1, 8, 15 and 22 of each cycle.

Tasigna®(nilotinib):: 50 mg, 150 mg and 200 mg capsules. Tasigna® capsules contain lactose monohydrate, crospovidone, poloxamer, colloidal silicon dioxide and magnesium. Orally; the capsules should be swallowed as a whole with water. No food should be consumed for 2 hours before the dose is taken and for at least one hour thereafter. For patients who are unable to swallow capsules, the content of each capsule may be dispersed in one teaspoon of apple sauce or compote or nonfat plain yogurt and should be taken immediately. Not more than one teaspoon of apple sauce / yogourt, and no food other than apple sauce or nonfat plain yogurt must be used.

Nilotinib

Vinblastine: 3 to 6 mg/m2 once weekly in a 15-minute infusion, on Days 1, 8, 15 and 22 of each cycle.
Each 28-day cycle is repeated on Day 29/Day 1. No intra-patient doseescalation is permitted. Dose allocation will be centrally defined, based on toxicity observed in patients previously evaluated. Every new patient will be treated at the best current recommended dose, i.e. the dose associated with an estimated level of toxicity that is judged acceptable (20% DLT). At least two patients fully observed with no DLT are requested at a given dose level before dose escalation.

Study Of Vinblastine in Combination With Nilotinib in Children, Adolescents and Young Adults

PHASE I-II STUDY OF VINBLASTINE IN COMBINATION WITH NILOTINIB IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH REFRACTORY OR RECURRENT LOW-GRADE GLIOMA

Dose-Limiting Toxicity (DLT), assessed over the first 28-day cycle, defined as
Grade > 3 neutropenia (<1 x 109/L) for more than 7 days;
Grade > 2 thrombopenia (<75 x 109/L) or thrombocytopenia requiring transfusions for more than 7 days.
Grade 3 or grade 4 non-hematological toxicity, excluding grade 3 nausea, vomiting, fever, and hepatic toxicity that is rapidly reversible (i.e. returns to < 2.5 x ULN within 2 weeks after study drug discontinuation), and symptoms that are related to tumor progression.

optic nerve glioma/tyrosine

Study of Vinblastine in Combination With Nilotinib in Children, Adolescents, and Young Adults

Study Of Vinblastine in Combination With Nilotinib in Children, Adolescents and Young Adults

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