Study in Plerixafor and Granulocyte-colony Stimulating Factor Patients With Relapse Acute Myeloid Leukemia
Phase 1
Terminated
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT01455025
- Lead Sponsor
- French Innovative Leukemia Organisation
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Plerixafor granulocyte-colony stimulating factor Plerixafor granulocyte-colony stimulating factor 4 steps of plerixafor doses from 240 to 480 microgram/kg per day concomitant with GCSF and chemotherapy 3 to 6 evaluable patients will be enrolled at each dose level in a modified 3 + 3 design.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 9 months overal survival
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
Trial Locations
- Locations (1)
Xavier THOMAS
🇫🇷Lyon, France