NCT02319135: FLUGAZA

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.

Completed Phase 3 Last updated 3 April 2020

What this trial tests

Phase 3 trial testing Azacitadine in Acute Myeloid Leukemia in 289 participants. Completed in 28 October 2019.

Timeline

1 October 2014

Primary endpoint
28 October 2018

28 October 2019

Quick facts

Lead sponsor	PETHEMA Foundation
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	289
Start date	1 October 2014
Primary completion	28 October 2018
Estimated completion	28 October 2019
Sites	1 location across Spain

Drugs / interventions tested

• Azacitadine — full drug profile →
• Fludarabine (FLUDARABINE) — full drug profile →
• Cytarabine — full drug profile →
• Lenograstim
• Filgastrim — full drug profile →

Conditions studied

• Acute Myeloid Leukemia — all drugs for Acute Myeloid Leukemia →

Sponsor

PETHEMA Foundation

Who can join

65 and older, any sex, with Acute Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• 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).

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
   Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
2. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.
   Nepali K, Liou JP. · · 2021 · cited 122× · PMID 33840388 · DOI 10.1186/s12929-021-00721-x
3. Blastic plasmacytoid dendritic cell neoplasm frequently shows occult central nervous system involvement at diagnosis and benefits from intrathecal therapy.
   Martín-Martín L, Almeida J, Pomares H, González-Barca E, et al · · 2016 · cited 60× · PMID 26840087 · DOI 10.18632/oncotarget.7101
4. The Mutational Landscape of Acute Myeloid Leukaemia Predicts Responses and Outcomes in Elderly Patients from the PETHEMA-FLUGAZA Phase 3 Clinical Trial.
   Ayala R, Rapado I, Onecha E, Martínez-Cuadrón D, et al · · 2021 · cited 11× · PMID 34070172 · DOI 10.3390/cancers13102458
5. Hypomethylating agent-based therapies in older adults with acute myeloid leukemia - A joint review by the Young International Society of Geriatric Oncology and European Society for Blood and Marrow Transplantation Trainee Committee.
   Neuendorff NR, Gagelmann N, Singhal S, Meckstroth S, et al · · 2023 · cited 9× · PMID 36435726 · DOI 10.1016/j.jgo.2022.11.005
6. Biallelic TET2 mutations confer sensitivity to 5'-azacitidine in acute myeloid leukemia.
   Stölzel F, Fordham SE, Nandana D, Lin WY, et al · · 2023 · cited 8× · PMID 36480300 · DOI 10.1172/jci.insight.150368
7. The transcriptomic landscape of elderly acute myeloid leukemia identifies <i>B7H3</i> and <i>BANP</i> as a favorable signature in high-risk patients.
   Villar S, Ariceta B, Agirre X, Urribarri AD, et al · · 2022 · cited 6× · PMID 36505804 · DOI 10.3389/fonc.2022.1054458
8. Data-driven flow cytometry classification of blast differentiation in older patients with acute myeloid leukemia.
   Simoes C, Gonzalez C, Vergez F, Sarry A, et al · · 2024 · cited 1× · PMID 40453058 · DOI 10.1016/j.bneo.2024.100027