relapsed/refractory AML (pediatric)
Conditions
Interventions
Combination treatment is allowed only for Course 1: An adapted regimen is used to combine Vyxeos®/CPX-351 given at day 1, 3, 5 with clofarabine given at day 2-6.
- Vyxeos®/CPX-351 will be infused on d
Sponsors
Princess Máxima Center for pediatric oncology
Eligibility
Inclusion criteria
Inclusion criteria: We will include pediatric patients =1 year and 6 weeks • The patient must have a radioisotope GFR = 70mL/min/1.73 m2. • Liver function: serum bilirubin =3 × upper limit of normal (ULN) and aspartate transaminase (AST)/alanine transaminase (ALT) =5×ULN • Adequate cardiac function (defined as shortening fraction =28% or ejection fraction =50%) • No evidence of a currently uncontrolled bacterial, viral or parasitic infection • No evidence of a fungal infection, defined as either: - Pulmonary infiltrates suggestive of a fungal infection at HR-CT (within 3 weeks prior to enrollment) - Positive Aspergillus serum test (galactomannan), according to local laboratory practice (within 3 weeks prior to enrollment) • No evidence of isolated extramedullary relapse, including isolated CNS-relapse • No evidence of CNS3 or symptomatic CNS leukemia • No presence of Down Syndrome • No evidence of relapsed/refractory acute promyelocytic leukemia (APL) • No use of any anticancer therapy within 2 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy (note: hematological toxicities do not need to be considered since the patient has overt leukemia) • No history of prior veno-occlusive disease (VOD) • No known hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin Other: • For female patients with childbearing potential, a negative test for pregnancy is to be performed before entry on study. • Male and female patients must use a highly effective contraceptive method during the study and for a minimum of 6 months after study treatment. • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule is required; those conditions should be discussed with the patient before registration in the trial. • Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Concomitant treatments: • Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in the protocol is not allowed. • GCSF will not be used for priming and no routine GCSF support is allowed during the 1st course, except for life-threatening infections. Additional criteria: • At least 6 patients must be enrolled with an M3 or a WBC count >10x109/L with blasts
Exclusion criteria
Exclusion criteria: see inclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish the recommended phase 2 dose of Vyxeos®/CPX-351 in combination with clofarabine in children with relapsed/refractory AML | — |
Secondary
| Measure | Time frame |
|---|---|
| • To determine the safety and tolerability of this combination • To determine the (preliminary) efficacy in terms of the hematological remission rate in these patients as determined by morphology with flow cytometric confirmation. • To describe the durability of response, including the number of patients that undergo stem- cell transplant after re-induction with this regimen | — |
Contacts
Public ContactMiriam Stumpf
Prinses Máxima Centrum voor kinderoncologie
Outcome results
None listed