Relapsed/refractory leukemia
Conditions
Interventions
Children will be treated orally with midostaurin (25mg/ml). As long as they
experience benefits from treatment with midostaurin, they can continue to take
it. De respons evaluation takes place every
Sponsors
Novartis
Eligibility
Age
2 Years to 17 Years
Inclusion criteria
Inclusion criteria: 1. Patients must have a documented diagnosis of one of the following leukemias: • MLL-rearranged ALL, refractory to standard induction treatment or in first or subsequent relapse • FLT3-mutated AML refractory to standard induction (after failure of at least 2 different induction chemotherapy regimens) or refractory to reinduction at 1st relapse (after failure of the first re-induction course), or in second or greater relapse 2. Patients must be less than 18 years of age and >=3 months of age. 3. Patients must have a Lansky/Karnofsky performance status >= 60. 4. Patients must have the following laboratory values reflecting appropriate organ function: • AST and ALT
Exclusion criteria
Exclusion criteria: 1. Patients with symptomatic leukemic CNS involvement. 2. Patients with isolated extramedullary leukemia. 3. Patients must have recovered from prior cytotoxic chemotherapy, and a minimum wash-out time of previous chemotherapy of 72 hours should be taken into account. For intrathecal chemotherapy, the minimum wash-out time is 48 hours 4. Patients who had prior allogeneic, syngeneic or autologous bone marrow or stem cell transplant less than 2 months from Day 1 5. Patients who have received any investigational agent within 30 days or 5 half lives, whichever is greater, prior to Day 1. 6. Patients who have had prior treatment with a FLT3 inhibiting drug or investigational agent, except for sorafenib 7. Use of CYP3A4/5 enzyme inducing or inhibiting drugs or CYP3A4/5 enzyme inducing or inhibiting herbal supplements while on study treatment 8. The use of corticosteroids while on study drug (exceptions are noted in the protocol section 6.6.5) 9. Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin or bone marrow biopsy), within 14 days of Day 1. 10. Patients with any other known disease concurrent severe and/or uncontrolled medical condition (e.g. cardiovascular disease including congestive heart failure or active uncontrolled infection) which could compromise participation in the study. 11. Patients with an abnormal chest X-ray and/or any pulmonary infiltrate including those suspected to be of infectious origin. In particular, patients with resolution of clinical symptoms of pulmonary infection but with residual pulmonary infiltrates on chest x-ray are not eligible until pulmonary infiltrates have completely resolved. 12. Patients with known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of midostaurin, including active graft-versus-host disease of the liver or the gut. 13. Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis. 14. Patients with a left ventricular shortening fraction = 450 ms, PR >=200 msec, QRS complex >=110 msec, at screening or prior to first dosing • Any cardiac conduction abnormality • Any morphologic abnormality • Any ST/T wave abnormality • Any atrial or ventricular arrhythmia 16. Female patients who are pregnant or breast feeding or patients of reproductive potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial by both sexes, if applicable. 17. Males of reproductive potential unwilling to comply with contraceptive requirements 18. Patients/parents unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the maximum tolerated dose (MTD) or to identify the recommended dose for expansion (RDE) for two age groups (>=3 months to 2years to | — |
Secondary
| Measure | Time frame |
|---|---|
| • To characterize the safety and tolerability of midostaurin, including acute and chronic toxicities • To characterize the population PK of single and repeated doses of midostaurin and its metabolite(s), • To determine the response rates, time to relapse and overall survival of patients treated with midostaurin. | — |
Countries
Netherlands
Outcome results
None listed