acute myeloid leukemia in children relapse refactory
Conditions
Interventions
Patients will be treated with a combination of clofarabine, liposomal daunorubicina nd cytarabine. Clofarabine is the IMP in this study.
Sponsors
Erasmus MC, Rotterdam, The Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: 1. 2nd relapse of AML; 2. Refractory AML in 1st relapse (defined as ≥ 20% blasts in the bone marrow after the 1st course of re-induction therapy according to the AML 2001/01 protocol); 3. 1st early relapse (relapse within one year from initial diagnosis) of AML (only when the Relapsed AML 2001/01 study is closed); 4. ≤ 18 years old at initial diagnosis; 5. Lansky play score > 60; or Karnofsky performance status > 60; 6. Life expectancy  6 weeks; 7. Calculated creatinine clearance ≥ 90 ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys; 8. Liver function: A. Serum bilirubin ≤1.5 × upper limit of normal (ULN); B. Aspartate transaminase (AST)/alanine transaminase (ALT) <=2.5 × ULN; C. Alkaline phosphatase <= 2.5 × ULN. 9. Able to comply with scheduled follow-up and with management of toxicity; 10. For female patients with childbearing potential, a negative test for pregnancy is to be considered before entry on study; 11. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment; 12. Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations.
Exclusion criteria
Exclusion criteria: 1. Isolated extramedullary relapse, including isolated CNS-relapse; 2. Symptomatic CNS leukemia in case of combined relapse; 3. Relapsed/refractory acute promyelocytic leukemia (APL); 4. Relapsed/refractory myeloid leukemia of Down Syndrome (ML DS); 5. Other serious illnesses or medical conditions; 6. Current uncontrolled infection; 7. Evidence of cardiac dysfunction (shortening fraction below 28%); 8. Pregnant or lactating patients; 9. 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); 10. History of prior veno-occlusive disease (VOD); 11. Hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin; 12. 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; 13. GCSF will not be used for priming and no routine GCSF support is allowed during the 1st course, except for life-threatening infections; 14. In case of non-symptomatic CNS-involvement, intrathecal therapy is allowed according to investigator's discretion. It is not allowed to give intrathecal therapy prior to treatment with clofarabine, as we do not know if this can be done without safety concerns. Hence, this should be delayed to day +7 of treatment, which will allow us to assess the CSF penetration of clofarabine (clofarabine CSF levels and early response). In case of neurotoxicity experienced during the IV treatment, the intrathecal may need to be further delayed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish the recommended dose of clofarabine in combination with cytarabine and liposomal daunorubicin (DaunoXome®) in children with relapsed/refractory AML, based on the FLAG regimen as used in the Relapsed AML 2001/01 study. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To determine the safety and tolerability of this combination; 2. To determine (preliminary) efficacy in terms of the hematological remission rate in these patients; 3. To describe the durability of response, including the number of patients that undergo stem-cell transplant after re-induction with this regimen; 4. To describe the pharmacokinetics of clofarabine in combination with cytarabine and liposomal daunorubicin; 5. To preliminary assess the CSF blast disappearance, and the CSF-levels of clofarabine. | — |
Contacts
Public ContactC.M. Zwaan
Outcome results
None listed