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

This study has been terminated.
(no recruitment on time)
Sponsor:
Collaborators:
Acute Leukemia French Association
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
French Innovative Leukemia Organisation
ClinicalTrials.gov Identifier:
NCT01455025
First received: June 24, 2011
Last updated: March 15, 2016
Last verified: August 2015
  Purpose
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 .

Condition Intervention Phase
Acute Myeloid Leukemia
Drug: Plerixafor granulocyte-colony stimulating factor
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1, Dose Escalation Study of Plerixafor in Combination With Induction and Consolidation Chemotherapy in Patients With Relapsed Acute Myeloid Leukemia

Resource links provided by NLM:


Further study details as provided by French Innovative Leukemia Organisation:

Primary Outcome Measures:
  • maximal tolerated dose [ Time Frame: 40 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • safety and tolerability of plerixafor in combination with granulocyte-colony stimulating factor and chemotherapy [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    Number of Adverse Events and Serious Adverse Events :examined at each dose level by the Independent Data safety Monitoring Board

  • Efficacy of plerixafor on leukemic blasts [ Time Frame: 10 Days ] [ Designated as safety issue: Yes ]
    study of the drop of leukemic blasts blood rate

  • Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    -Minimal Residual Disease level after first consolidation

  • Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine [ Time Frame: 5 weeks ] [ Designated as safety issue: Yes ]
    - Time to remission

  • Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    -Rate of patients able to proceed to hematopoietic stel cell transplantation

  • Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    -disease free survival

  • Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    -event free survival

  • Efficacy of combination plerixafor with granulocyte-colony stimulating factor, Daunorubicin and Cytarabine [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
    overal survival


Enrollment: 11
Study Start Date: January 2012
Study Completion Date: August 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

Other Name: Plerixafor G CSF

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

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01455025

Locations
France
Xavier THOMAS
Lyon, France, 69437
Sponsors and Collaborators
French Innovative Leukemia Organisation
Acute Leukemia French Association
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Xavier THOMAS, MD PD ALFA
Principal Investigator: Didier BOUSCARY, MD PD French Innovative Leukemia Organisation
  More Information

Additional Information:
Responsible Party: French Innovative Leukemia Organisation
ClinicalTrials.gov Identifier: NCT01455025     History of Changes
Other Study ID Numbers: Primal study 
Study First Received: June 24, 2011
Last Updated: March 15, 2016
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French Innovative Leukemia Organisation:
Plerixafor granulocyte-colony stimulating factor
Chemotherapy in relapse
Acute Myeloid Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Lenograstim
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 23, 2016