This study aims to investigate the safety and efficacy of clofarabine, given in combination with cytarabine and liposomal daunorubicin, in the treatment of children with relapsed/refractory acute myeloid leukemia (AML)

• Conditions: Relapsed/refractory acute myeloid leukemia; MedDRA version: 14.0Level: LLTClassification code 10066638Term: Acute myeloid leukemia progressionSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.0Level: LLTClassification code 10060558Term: Acute myeloid leukemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2009-009457-13-NL
• Lead Sponsor: Erasmus MC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-05-07
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 28

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

• 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified