study in plerixafor and granulocyte-colony stimulating factor patients with relapse acute myeloid leukemia

Conditions: Acute Myeloid Leukemia

Summary: this is a phase 1, dose escalation study of plerixafor in combination with granulocyte-colony stimulating factor , daunorubicin and cytarabine in adults patients with relapsed acute myeloid leukemia .

the primary objective is to determine the maximal tolerated dose and recommended phase 2 dose of plerixafor when used in combination with granulocyte-colony stimulating factor, daunorubicin and cytarabine during induction therapy then determine the tolerability of plerixafor administered in combination with g-csf and cytarabine during consolidation therapy.

Eligibility criteria:
inclusion criteria: * patients with acute myeloid leukemia in first relapse with first response duration \> 9 months. * 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 exclusion criteria: * 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 purinethol. * 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 seizures. * 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 study entry. * pregnancy or breastfeeding * adult patient protected by law * concurrent treatment with any other anti-cancer therapy except hydroxyurea

Keywords: plerixafor granulocyte-colony stimulating factor chemotherapy in relapse acute myeloid leukemia