Study in Plerixafor and Granulocyte-colony Stimulating Factor Patients With Relapse Acute Myeloid Leukemia (PRIMAL)
March 15, 2016 updated by: French Innovative Leukemia Organisation
A Phase 1, Dose Escalation Study of Plerixafor in Combination With Induction and Consolidation Chemotherapy in Patients With Relapsed Acute Myeloid Leukemia
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 .
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
11
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Lyon, France, 69437
- Xavier THOMAS
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: 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.
|
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
maximal tolerated dose
Time Frame: 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.
|
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
Time Frame: 9 months
|
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
Time Frame: 10 Days
|
study of the drop of leukemic blasts blood rate
|
10 Days
|
|
Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
Time Frame: 2 months
|
-Minimal Residual Disease level after first consolidation
|
2 months
|
|
Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
Time Frame: 5 weeks
|
- Time to remission
|
5 weeks
|
|
Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
Time Frame: 3 months
|
-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
Time Frame: 9 months
|
-disease free survival
|
9 months
|
|
Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
Time Frame: 9 months
|
-event free survival
|
9 months
|
|
Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine
Time Frame: 9 months
|
overal survival
|
9 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Xavier THOMAS, MD PD, ALFA
- Principal Investigator: Didier BOUSCARY, MD PD, French Innovative Leukemia Organisation
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2012
Primary Completion (Actual)
March 1, 2015
Study Completion (Actual)
August 1, 2015
Study Registration Dates
First Submitted
June 24, 2011
First Submitted That Met QC Criteria
October 17, 2011
First Posted (Estimate)
October 19, 2011
Study Record Updates
Last Update Posted (Estimate)
March 16, 2016
Last Update Submitted That Met QC Criteria
March 15, 2016
Last Verified
August 1, 2015
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Primal study
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.