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

NCT ID: NCT01455025

Last Updated: 2016-03-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-08-31

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Plerixafor granulocyte-colony stimulating factor

Intervention Type: DRUG

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

Interventions

Plerixafor 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

Intervention Type: DRUG

Other Intervention Names

Plerixafor G CSF

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Acute Leukemia French Association

OTHER

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

French Innovative Leukemia Organisation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier THOMAS, MD PD

Role: PRINCIPAL_INVESTIGATOR

ALFA

Didier BOUSCARY, MD PD

Role: PRINCIPAL_INVESTIGATOR

French Innovative Leukemia Organisation

Locations

Xavier THOMAS

Lyon, , France

Countries

France

Related Links

http://www.filo-leucemie.org

FILO website

Other Identifiers

Primal study

Identifier Type: -

Identifier Source: org_study_id