Acute Myeloid Leukemia
Conditions
Keywords
Plerixafor granulocyte-colony stimulating factor, Chemotherapy in relapse, Acute Myeloid Leukemia
Brief 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 .
Detailed description
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.
Interventions
DRUGPlerixafor granulocyte-colony stimulating factor
Induction phase Plerixafor IV from D1 to D3 and from D8 to D10, granulocyte-colony stimulating factor IV 5 μg/kg/day from D1 to D10, Intravenous daunorubicin 60 mg/m2/day from D1 to D3 Cytarabine 500 mg/m2/day continuous infusion over 24h from D1 to D3 followed by cytarabine 2-hour bolus of 1000 mg/m2/12h from D8 to D10. Consolidation phase Plerixafor at D1, D3 and D5, granulocyte-colony stimulating factor IV 5 μg/kg/day from D1 to D5, Cytarabine continuous infusion of 3-h bolus of 3000 mg/m2/12h D1, D3 and D5
Sponsors
Acute Leukemia French Association
Genzyme, a Sanofi Company
French Innovative Leukemia Organisation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| maximal tolerated dose | 40 days | 4 steps of plerixafor doses from 240 to 480 microgram per kilogram per day concomitant with granulocyte-colony stimulating factor and chemotherapy Three to 6 evaluable patients will be enrolled at each dose level in a modified 3 + 3 design. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| safety and tolerability of plerixafor in combination with granulocyte-colony stimulating factor and chemotherapy | 9 months | Number of Adverse Events and Serious Adverse Events :examined at each dose level by the Independent Data safety Monitoring Board |
| Efficacy of plerixafor on leukemic blasts | 10 Days | study of the drop of leukemic blasts blood rate |
| Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine | 2 months | -Minimal Residual Disease level after first consolidation |
Countries
France
Outcome results
None listed