Relapsed/refractory acute myeloid leukemia MedDRA version: 14.0 Level: LLT Classification code 10066638 Term: Acute myeloid leukemia progression System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.0 Level: LLT Classification code 10060558 Term: Acute myeloid leukemia recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Evoltra 1 mg/ml concentrate for solution for infusion
Product Name: Evoltra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: CLOFARABINE
CAS Number: 123318-8
Sponsors
Erasmus MC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 2nd relapse of AML • refractory AML in 1st relapse (defined as = 20% blasts in the bone marrow after the 1st course of standard re-induction therapy) • 1st early relapse (relapse within one year from initial diagnosis) of AML • = 18 years old at initial diagnosis • Lansky play score = 60; or Karnofsky performance status = 60 • Life expectancy =6 weeks • 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. • Liver function: Serum bilirubin =1.5 × upper limit of normal (ULN) Aspartate transaminase (AST)/alanine transaminase (ALT) =2.5 × ULN Alkaline phosphatase =2.5 × ULN • Able to comply with scheduled follow-up and with management of toxicity. • For female patients with childbearing potential, a negative test for pregnancy is to be considered before entry on study • Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment. • Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations Patient group specific for dose level 5: •Newly diagnosed 1st relapse of AML: only patients with early relapses occurring within 1 year of initial diagnosis are eligible Are the trial subjects under 18? yes Number of subjects for this age range: 39 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Isolated extramedullary relapse, including isolated CNS-relapse • Symptomatic CNS leukemia in case of combined relapse • Relapsed/refractory acute promyelocytic leukemia (APL) • Relapsed/refractory myeloid leukemia of Down Syndrome (ML DS) • Other serious illnesses or medical conditions • Evidence of fungal infection by: -Evidence of pulmonary infiltrates suggestive of a fungal infection at HR-CT (within 3 weeks prior to enrollment); -A positive Aspergillus serum test (galactomannan), according to local laboratory practice (within 3 weeks prior to enrollment) • Evidence of cardiac dysfunction (shortening fraction below 28%) • Pregnant or lactating patients Prior or current history: • 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). • History of prior veno-occlusive disease (VOD) • Hypersensitivity to cytarabine, clofarabine or liposomal daunorubicin Specific for dose level 5: • Prior stem-cell transplant in CR1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the recommended dose of clofarabine in combination with cytarabine and liposomal daunorubicin (DaunoXome®) in children with relapsed/refractory AML. Note: dosages of cytarabine and liposomal daunorubicin should be comparable to those used in the current Relapsed AML 2001/01 study (i.e. in the context of the FLAG/liposomal daunorubicin regimen).;Secondary Objective: - To determine the safety and tolerability of this combination - To determine (preliminary) efficacy in terms of the hematological remission rate in these patients - To describe the durability of response, including the number of patients that undergo stem-cell transplant after re-induction with this regimen - To describe the pharmacokinetics of clofarabine in combination with cytarabine and liposomal daunorubicin - To preliminary assess the CSF blast disappearance, and the CSF-levels of clofarabine ;Primary end point(s): To identify the recommended dose of the combination of clofarabine, cytarabine and liposomal daunorubicin in relapsed/refractory AML, hence to identify dose-limiting toxicities and the MTD.;Timepoint(s) of evaluation of this end point: after cycle 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - safety and tolerability of this combination - (preliminary) efficacy in terms of the hematological remission rate in these patients - durability of response, including the number of patients that undergo stem-cell transplant after re-induction with this regimen - pharmacokinetics of clofarabine in combination with cytarabine and liposomal daunorubicin - assess the CSF blast disappearance, and the CSF-levels of clofarabine ;Timepoint(s) of evaluation of this end point: after cycle 1 | — |
Countries
Austria, Czech Republic, France, Germany, Netherlands
Contacts
Public ContactMichel Zwaan
Erasmus MC
Outcome results
None listed