Study in Plerixafor and Granulocyte-colony Stimulating Factor Patients With Relapse Acute Myeloid Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1, Dose Escalation Study of Plerixafor in Combination With Induction and Consolidation Chemotherapy in Patients With Relapsed Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Plerixafor granulocyte-colony stimulating factor


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plerixafor granulocyte-colony stimulating factor<br>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. | Drug: Plerixafor granulocyte-colony stimulating factor<br>* 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<br>* Other names: Plerixafor G CSF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximal tolerated dose | 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. | 40 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of plerixafor in combination with granulocyte-colony stimulating factor and chemotherapy | Number of Adverse Events and Serious Adverse Events :examined at each dose level by the Independent Data safety Monitoring Board | 9 months | 
| Efficacy of plerixafor on leukemic blasts | study of the drop of leukemic blasts blood rate | 10 Days | 
| Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine | -Minimal Residual Disease level after first consolidation | 2 months | 
| Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine | - Time to remission | 5 weeks | 
| Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine | -Rate of patients able to proceed to hematopoietic stel cell transplantation | 3 months | 
| Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine | -disease free survival | 9 months | 
| Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine | -event free survival | 9 months | 
| Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine | overal survival | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plerixafor granulocyte-colony stimulating factor, Chemotherapy in relapse, Acute Myeloid Leukemia