Clinical trial NCT01455025: Study in Plerixafor and Granulocyte-colony Stimulating Factor Patients With Relapse Acute Myeloid Leukemia
Official title: A Phase 1, Dose Escalation Study of Plerixafor in Combination With Induction and Consolidation Chemotherapy in Patients With Relapsed Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: Plerixafor granulocyte-colony stimulating factor
Chemotherapy in relapse
Acute Myeloid Leukemia
Lead sponsor: French Innovative Leukemia Organisation
Sponsor class: OTHER
Collaborators: name: Acute Leukemia French Association
name: Genzyme, a Sanofi Company
First posted: 2011-10-19
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: maximal tolerated dose
timeFrame: 40 days
Secondary outcomes:
measure: safety and tolerability of plerixafor in combination with granulocyte-colony stimulating factor and chemotherapy
timeFrame: 9 months
measure: Efficacy of plerixafor on leukemic blasts
timeFrame: 10 Days
measure: Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
timeFrame: 2 months
measure: Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
timeFrame: 5 weeks
measure: Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
timeFrame: 3 months
measure: Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
timeFrame: 9 months
measure: Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
timeFrame: 9 months
measure: Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
timeFrame: 9 months
Other outcomes:
Locations:
city: Lyon
country: France
facility: Xavier THOMAS
Study officials:
affiliation: ALFA
name: Xavier THOMAS, MD PD
role: PRINCIPAL_INVESTIGATOR
affiliation: French Innovative Leukemia Organisation
name: Didier BOUSCARY, MD PD
role: PRINCIPAL_INVESTIGATOR
References: