A Phase 1, Dose Escalation Study of Plerixafor in Combination With Induction and Consolidation Chemotherapy in Patients With Relapsed Acute Myeloid Leukemia
- Patients with Acute Myeloid Leukemia in first relapse with first response duration >
- Age between 18 and 65 years.
- Treatment with hydroxyurea or purinethol is allowed if discontinued at least 24 hours
before the start of study treatment.
- White blood count less than 30 x 109/L
- Left ventricular ejection fraction more than 50% on echocardiography or multigated
acquisition scan or similar radionuclide angiographic scan.
- Total bilirubin less than 1.5 x upper limit of normal= ULN or AST and ALT less
than 2.5 x ULN or gammaGT less than 2.5 x ULN.
- Serum creatinine less than 1.5 x ULN and/or creatinine clearance more than 50 ml/mn.
- ECOG performance status less than 2
- Absence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule.
- Absence of pregnancy or lactation
- Affiliated to French social security system or similar
- Signed informed consent
- AML evolving from MPD and/or secondary AML
- Patients treated with more than 270 mg/m2 of daunorubicin during first line therapy.
- Have any of the following within the last 9 months :
- Unstable supraventricular arrhythmia or patient with a pace-maker
- Any ventricular arrhythmia
- Congestive heart failure
- Myocardial infarction, ischemia, stable coronary disease or angina pectoris
- Syncope with a known cardiovascular etiology
- Known hypersensitivity or contra-indication to drugs used in the protocol = G-CSF,
daunorubicin, cytarabine or to excipients.
- Previous treatment with plerixafor.
- Previous hematopoietic stem cell transplantation = Allologous or autologous.
- White blood count more than 30 x 109/L despite treatment with hydroxyurea or
- Treatment with chemotherapy or G-CSF within 3 months of screening.
- Uncontrolled active infection.
- Uncontrolled arrythmia
- Grade more than 3 renal dysfunction with serum creatinine more than 1.5 x ULN and/or
creatinine clearance less than 50 ml/mn.
- Significant neurologic grade more than 2 or psychiatric disorder, dementia or
- Clinical symptoms suggesting active central nervous system leukemia.
- Pre-existing disorder predisposing the patient to serious or life-threatening
infections = cystic fibrosis, congenital or acquired immunodeficiency, bleeding
disorder or cytopenia
- Thrombocytopenia refractory to platelet transfusion
- Anticoagulant therapy
- Severe complications of leukemia such as uncontrolled bleeding, pneumonia with
hypoxia or shock or disseminated intravascular coagulation.
- Thrombocytopenia refractory to platelet transfusion.
- Prior total body irradiation more than 10 Gy.
- Known HIV, Hepatitis B or C positivity.
- Participation into a clinical study of an investigational agent within 14 days before
- Pregnancy or breastfeeding
- Adult patient protected by law
- Concurrent treatment with any other anti-cancer therapy except hydroxyurea