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

April 3, 2020 updated by: PETHEMA Foundation

A PHASE III, MULTICENTRE, RANDOMIZED, OPEN LABEL CLINICAL TRIAL OF AZACYTIDINE (VIDAZA®) VERSUS FLUDARABINE AND CYTARABINE (FLUGA SCHEME) IN ELDERLY PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, randomized 1:1, open, and at national level, Phase III clinical trial.

This study will be conducted in 3 phases of different duration:

  1. Selection phase (up to 14 days from the signature of informed consent): informed consent and review of the inclusion and exclusion criteria performing the relevant assessments.
  2. Treatment Phase (from the start of treatment until the end of cycle 9): Induction phase (3 cycles) and consolidation phase (cycles 4-9). Study visits during treatment will be weekly during the induction phase (first 3 cycles) and every 2 weeks until the end of the consolidation phase.
  3. Follow-up phase: monthly monitoring will be performed on all patients until they have completed a minimum of 2 years from the start of treatment, whether or not they continue receiving azacitidine cycles or Mini-Fluga according to the protocol. Following these 24 months, follow-up will be carried out at least quarterly. Patients suffering disease progression or relapse of the disease, or being early withdrawn due to any of the reasons specified in the protocol will be followed-up for survival until the end of the study or until the death of all patients, whichever comes first.

Study Type

Interventional

Enrollment (Actual)

289

Phase

  • Phase 3

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

  • Spain
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe

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

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. - Having voluntarily given informed consent before performing any test that is not part of

    routine care of patients.

  2. - Age greater than or equal to 65.
  3. - Morphological diagnosis of non-promyelocytic AML according to the WHO criteria.
  4. - Newly diagnosed AML.
  5. - ECOG performance status <4.
  6. - Ability and willingness to comply with the schedule of study visits.

Exclusion Criteria:

  1. - Genetic diagnosis of acute promyelocytic leukemia.

  2. - 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.

  3. - Serum creatinine ≥ 250 mmol / l (≥ 2.5 mg/dL) (unless attributed to AML).
  4. - Bilirubin, alkaline phosphatase or ALT > 5 times the value of the upper limit of normal (unless attributed to AML) .
  5. - 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.
  6. - Other active concomitant malignancy or whose remission is less than one year from the screening day (except carcinoma in situ).
  7. - Presence of any psychiatric illness or medical condition that, in the investigator's opinion, prevents the subject participation in the study.
  8. - Life expectancy less than X months.
  9. - Inability of the patient or his legal representative to understand and voluntarily sign the informed consent form.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: fludarabine cytarabine

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy (overall survival (OS) attained without increasing the therapy-related toxicity or decreasing the patients QoL.
Time Frame: 4 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy (Event free survival (EFS)
Time Frame: 4 years
Event free survival (EFS)
4 years
Efficacy (Duration of remission.)
Time Frame: 4 years
Duration of remission.
4 years
Efficacy (Overall survival) Efficcacy
Time Frame: 3 years
Overall survival at 2nd and 3rd year.
3 years
Safety (Compare hematologic and non-hematologic toxicity)
Time Frame: 3 years
Compare hematologic and non-hematologic toxicity in both arms.
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Collaborators

Dynamic Solutions

Investigators

  • Principal Investigator: Pau Montesinos, Dr, PETHEMA Foundation

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.

General Publications

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 (Actual)

October 1, 2014

Primary Completion (Actual)

October 28, 2018

Study Completion (Actual)

October 28, 2019

Study Registration Dates

First Submitted

December 10, 2014

First Submitted That Met QC Criteria

December 17, 2014

First Posted (Estimate)

December 18, 2014

Study Record Updates

Last Update Posted (Actual)

April 6, 2020

Last Update Submitted That Met QC Criteria

April 3, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FLUGAZA

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.

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