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

Acute Myeloid Leukemia Clinical Trial

— PRIMAL  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01455025
• Other study ID #: Primal study
• Status: Terminated
• Phase: Phase 1
• First received: June 24, 2011
• Last updated: March 15, 2016
• Start date: January 2012
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: French Innovative Leukemia Organisation
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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 .

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 information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: August 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• 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

Locations

Country	Name	City	State
France	Xavier THOMAS	Lyon

Sponsors (3)

Lead Sponsor	Collaborator
French Innovative Leukemia Organisation	Acute Leukemia French Association, Genzyme, a Sanofi Company

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	Efficacy of plerixafor on leukemic blasts	study of the drop of leukemic blasts blood rate	10 Days	Yes
Secondary	Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine	-Minimal Residual Disease level after first consolidation	2 months	Yes
Secondary	Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine	- Time to remission	5 weeks	Yes
Secondary	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	Yes
Secondary	Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine	-disease free survival	9 months	Yes
Secondary	Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine	-event free survival	9 months	Yes
Secondary	Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine	overal survival	9 months	Yes

External Links

•   FILO website