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

Primary Purpose

Acute Myeloid Leukemia

Status

Completed

Phase

Phase 3

Locations

Spain

Study Type

Interventional

Intervention

Azacitadine

Fludarabine

Cytarabine

Lenograstim

Filgastrim

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

Sites / Locations

Hospital Universitari i Politècnic La Fe

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

fludarabine cytarabine

Azacitidine

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Efficacy (Event free survival (EFS)

Event free survival (EFS)

Efficacy (Duration of remission.)

Duration of remission.

Efficacy (Overall survival) Efficcacy

Overall survival at 2nd and 3rd year.

Safety (Compare hematologic and non-hematologic toxicity)

Compare hematologic and non-hematologic toxicity in both arms.

Full Information

NCT ID

NCT02319135

First Posted

December 10, 2014

Last Updated

April 3, 2020

Sponsor

PETHEMA Foundation

Collaborators

Dynamic Solutions

1. Study Identification

Unique Protocol Identification Number

NCT02319135

Brief Title

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

Acronym

FLUGAZA

Official Title

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.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2020

Overall Recruitment Status

Completed

Study Start Date

October 2014 (Actual)

Primary Completion Date

October 28, 2018 (Actual)

Study Completion Date

October 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PETHEMA Foundation

Collaborators

Dynamic Solutions

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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: 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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

289 (Actual)

8. Arms, Groups, and Interventions

Arm Title

fludarabine cytarabine

Arm Type

Active Comparator

Arm Description

Arm Title

Azacitidine

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Azacitadine

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Intervention Type

Drug

Intervention Name(s)

Lenograstim

Intervention Type

Drug

Intervention Name(s)

Filgastrim

Primary Outcome Measure Information:

Title

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

Description

Time Frame

4 years

Secondary Outcome Measure Information:

Title

Efficacy (Event free survival (EFS)

Description

Event free survival (EFS)

Time Frame

4 years

Title

Efficacy (Duration of remission.)

Description

Duration of remission.

Time Frame

4 years

Title

Efficacy (Overall survival) Efficcacy

Description

Overall survival at 2nd and 3rd year.

Time Frame

3 years

Title

Safety (Compare hematologic and non-hematologic toxicity)

Description

Compare hematologic and non-hematologic toxicity in both arms.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: - 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. Exclusion Criteria: - 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pau Montesinos, Dr

Organizational Affiliation

PETHEMA Foundation

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital Universitari i Politècnic La Fe

City

Valencia

ZIP/Postal Code

46026

Country

Spain

12. IPD Sharing Statement

Citations:

PubMed Identifier

34070172

Citation

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.

Results Reference

derived

Links:

URL

http://www.dynasolutions.com

Description

CRO

Learn more about this trial

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

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