Treatment of Relapsed or Refractory Acute Myeloblastic Leukemia

NCT01435343 | Completed Phase 1 DMC

• 1 other identifier: PLERIFLAG
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 10

Brief Summary

Second-line induction therapy with fludarabine, idarubicin, cytarabine,Granulocyte colony-stimulating factor (G-CSF) and plerixafor, in patients with relapsed or refractory Acute Myeloblastic Leukemia (AML) aged 65 or younger.

Conditions

Acute Myeloblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Efficacy in terms of number of complete responses

  1 year

Secondary Outcomes (1)

• Safety in terms of percentages of adverse events presented

  1 year

Interventions

fludarabine DRUG

30 mg/m2/day intravenously on days 1 to 4

Idarubicin DRUG

10 mg/m2/day intravenously on days 1 to 3

cytarabine DRUG

2 g/m2/day intravenously on days 1 to 4

G-CSF DRUG

5 μg/kg/day subcutaneously from days 1 to 4

plerixafor DRUG

intravenously from days 1 to 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML according to the WHO criteria
• Relapsed or refractory AML as defined below First relapse after standard treatment with duration of the first remission less than year
• Refractoriness to an induction cycle that includes cytarabine and anthracyclines
• Nonpromyelocytic leukemia (absence of t(15;17) or PML-RARα rearrangement and its variants)
• Peripheral blood blast cell count less than 50 x 109/L. Hydroxyurea and leukopheresis can be used to lower the blast count prior to beginning treatment
• Age ≤ 65 years and ≥ 18 years
• ECOG performance status of 0-2
• Provide signed written informed consent
• Be able to comply with study procedures and follow-up examinations
• Be nonfertile or agree to use birth control during the study through the end of last treatment visit
• Adequate renal and hepatic function as indicated by all of the following:
• Total bilirubin \<1.5 x Institutional Upper Limit of Normal (ULN); and AST and ALT \<2.5 xULN; and Serum creatinine \<1.0 mg/dL; if serum creatinine \<1.0 mg/dL, then, the estimated glomerular filtration rate (GFR) must be \<60 ml/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation - Minimal impairment of cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) \>40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening \>22% on echocardiography exam;

You may not qualify if:

• Diagnosis of acute promyelocytic leukemia (APL, French-American-British \[FAB\] classification M3 or WHO classification of APL with t(15;17)(q22;q12), (PML/RARalfa and variants)
• AML secondary to previous treatment for myelodysplastic syndrome (MDS)
• Peripheral blood blast cell count ≥ 50 x 109/L. Hydroxyurea and leukopheresis can be used to lower the blast count prior to beginning treatment
• Prior investigational treatment within 30 days prior to the first dose of study drug. If any investigational treatment has been received prior to this time point, drug related toxicities must have recovered to Grade 1 or less prior to first dose of study drug
• Prior hematopoietic stem cell transplant (HSCT) (previous autologous hematopoietic stem cell transplant is allowed)
• Investigational agent received within 5 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 1 or less prior to first dose of study drug
• Impaired renal and liver function as indicated by the following:
• Total bilirubin \> 1.5 x upper limit of normal (ULN) provided that this is not attributable to AML itself; or AST and ALT \> 2.5 xULN provided that this is not attributable to AML itself; or Serum creatinine \> 1.0 mg/dL provided that the estimated glomerular filtration rate (GFR) is ≤ 60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation
• \- Impaired cardiac function as measured by at least 1 of the following: Left ventricular ejection fraction (LVEF) \< 40% on multigated acquisition (MUGA) scan or radionuclide angiographic scan; or Left ventricular fractional shortening \< 22% on echocardiography exam;
• Poor overall condition ECOG 3-4
• Refusal to sign the informed consent
• Unable to comply with study procedures and follow-up examinations
• Psychiatric disorders that could interfere with consent, study participation or follow-up
• Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions:

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (10)

Hospital Universitari Germans Trials i Pujol

Badalona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau.

Barcelona, Spain

Location

Hospital Duran i Reynals - ICO L'Hospitalet

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Clínico Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitari La Fe

Valencia, Spain

Location

Related Publications (1)

• Martinez-Cuadron D, Boluda B, Martinez P, Bergua J, Rodriguez-Veiga R, Esteve J, Vives S, Serrano J, Vidriales B, Salamero O, Cordon L, Sempere A, Jimenez-Ubieto A, Prieto-Delgado J, Diaz-Beya M, Garrido A, Benavente C, Perez-Simon JA, Moscardo F, Sanz MA, Montesinos P; CETLAM and PETHEMA groups. A phase I-II study of plerixafor in combination with fludarabine, idarubicin, cytarabine, and G-CSF (PLERIFLAG regimen) for the treatment of patients with the first early-relapsed or refractory acute myeloid leukemia. Ann Hematol. 2018 May;97(5):763-772. doi: 10.1007/s00277-018-3229-5. Epub 2018 Feb 2.

  PMID: 29392425 DERIVED

Related Links

• CRO

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; Idarubicin; Cytarabine; Granulocyte Colony-Stimulating Factor; plerixafor

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2011
• First Posted: September 16, 2011
• Study Start: July 1, 2012
• Primary Completion: May 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 25, 2017

Record last verified: 2016-09

Locations

ES (10)