Azacytidine (Vidaza®) Versus Fludarabine and Cytarabine (Fluga Scheme) in Elderly Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT02319135 | Completed Phase 3 DMC

• 1 other identifier: FLUGAZA
• Study Type: interventional
• Target: 289
• Locations: 1 country
• Sites: 1

Brief Summary

The hypothesis is that the replacement of the standard fludarabine and cytarabine based therapy by azacytidine could result in an improvement of RFS and OS rates in the experimental arm. To fulfill the medical needs in such frail and elderly population, improvements in terms of atileukemic efficacy in the azacytidine experimental arm should be attained without increasing the therapy-related toxicity or decreasing the patients QoL.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Efficacy (overall survival (OS) attained without increasing the therapy-related toxicity or decreasing the patients QoL.

  To evaluate the overall survival (OS) in one year treatment with 2 first-line regimens in newly diagnosed elderly patients: 3 cycles of induction chemotherapy based on fludarabine and cytarabine (FLUGA scheme) followed by maintenance with reduced doses(Mini-FLUGA) (standard treatment arm) versus subcutaneous azacitidine cycles (experimental treatment arm).

  4 years

Secondary Outcomes (4)

• Efficacy (Event free survival (EFS)

  4 years

• Efficacy (Duration of remission.)

  4 years

• Efficacy (Overall survival) Efficcacy

  3 years

• Safety (Compare hematologic and non-hematologic toxicity)

  3 years

Study Arms (2)

fludarabine cytarabine

ACTIVE COMPARATOR

Priming with daily administration of subcutaneous G-CSF (lenograstim or filgrastim 5 mcg /kg / day, days -1, 1 and 2) (not given if hyperleukocytosis\> 25 x 109/l), followed by: * Oral fludarabine (40 mg/m2/day, days 1 to 5) and subcutaneous cytarabine (75mg/m2/day, days 1 to 5) (FLUGA scheme) (fludarabine and cytarabine only days 1 to 4 if age ≥75 years), OR * Fludarabine (25 mg/m2/day) and cytarabine (75 mg/m2/day infusion of 6 hours) on their intravenous formulations if the patient is hospitalized (patients with hyperleukocytosis or other unfavourable conditions). Treatment cycles every 28 days

Drug: Fludarabine; Drug: Cytarabine; Drug: Lenograstim; Drug: Filgastrim

Azacitidine

EXPERIMENTAL

Subcutaneous Azacitidine 75 mg/m2/day, days 1 to 7. Treatment cycles every 28 days.

Drug: Azacitadine

Interventions

Azacitadine DRUG

Azacitidine

Fludarabine DRUG

fludarabine cytarabine

Cytarabine DRUG

fludarabine cytarabine

Lenograstim DRUG

fludarabine cytarabine

Filgastrim DRUG

fludarabine cytarabine

Eligibility Criteria

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

You may qualify if:

• \- Having voluntarily given informed consent before performing any test that is not part of
• routine care of patients.
• \- Age greater than or equal to 65.
• \- Morphological diagnosis of non-promyelocytic AML according to the WHO criteria.
• \- Newly diagnosed AML.
• \- ECOG performance status \<4.
• \- Ability and willingness to comply with the schedule of study visits.

You may not qualify if:

• \- Genetic diagnosis of acute promyelocytic leukemia.
• \- Patients with AML secondary to myelodysplastic syndrome (MDS) or chronic myeloproloferative syndrome who have been previously treated with antileukemic agents
• (hypomethylating or standard chemotherapy). Treatment with hydroxyurea prior to randomization is allowed.
• \- Serum creatinine ≥ 250 mmol / l (≥ 2.5 mg/dL) (unless attributed to AML).
• \- Bilirubin, alkaline phosphatase or ALT \> 5 times the value of the upper limit of normal (unless attributed to AML) .
• \- Presence of an active and/or non controlled pathology different to AML which is severe and life-threatening, that in the investigator's opinion, prevents the subject participation in the study.
• \- Other active concomitant malignancy or whose remission is less than one year from the screening day (except carcinoma in situ).
• \- Presence of any psychiatric illness or medical condition that, in the investigator's opinion, prevents the subject participation in the study.
• \- Life expectancy less than X months.
• \- Inability of the patient or his legal representative to understand and voluntarily sign the informed consent form.

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Dynamic Solutions: collaborator

Study Sites (1)

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Related Publications (1)

• Ayala R, Rapado I, Onecha E, Martinez-Cuadron D, Carreno-Tarragona G, Bergua JM, Vives S, Algarra JL, Tormo M, Martinez P, Serrano J, Herrera P, Ramos F, Salamero O, Lavilla E, Gil C, Lopez Lorenzo JL, Vidriales MB, Labrador J, Falantes JF, Sayas MJ, Paiva B, Barragan E, Prosper F, Sanz MA, Martinez-Lopez J, Montesinos P, On Behalf Of The Programa Para El Estudio de la Terapeutica En Hemopatias Malignas Pethema Cooperative Study Group. The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial. Cancers (Basel). 2021 May 18;13(10):2458. doi: 10.3390/cancers13102458.

  PMID: 34070172 DERIVED

Related Links

• CRO

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; Cytarabine; Lenograstim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Pau Montesinos, Dr

  PETHEMA Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: December 18, 2014
• Study Start: October 1, 2014
• Primary Completion: October 28, 2018
• Study Completion: October 28, 2019
• Last Updated: April 6, 2020

Record last verified: 2020-04

Locations

ES (1)