Efficacy of 5-Aza for Post-Remission Therapy of Acute Myeloid Leukemia (AML) in Elderly Patients

A Randomized Study to Evaluate the Efficacy of 5-Aza for Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients

The present study aims to compare the efficacy of postremission maintenance therapy with 5-Aza versus best supportive care (BSC) in a cohort of AML patients aged >60 years, who have achieved complete remission (CR) following conventional induction ('3+7') and consolidation chemotherapy.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Vidaza 100 milligram (mg) injection; Other: Best Supportive Care

Detailed Description

The present study aims to compare the efficacy of postremission maintenance therapy with 5-Aza versus best supportive care (BSC) in a cohort of AML patients aged >60 years, who have achieved CR following conventional induction ('3+7') and consolidation chemotherapy to evaluate 2 an 5 year post-remission rates of Overall Survival and disease free survival between two arms

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Italy
  • Udine, Italy
    • A.O.U. di Udine Centro Trapianti e Terapie Cellulari
  • AL
    • Alessandria, AL, Italy
      • A.O. SS. Antonio e Biagio e Cesare Arrigo
  • AN
    • Ancona, AN, Italy
      • Ospedale Riuniti
  • AV
    • Avellino, AV, Italy
      • A.O. S. Giovanni Moscati
  • BA
    • Bari, BA, Italy
      • Policlinico Università di Bari
  • CS
    • Cosenza, CS, Italy
      • Ospedale L'Annunziata
  • CT
    • Catania, CT, Italy
      • Ospedale Ferrarotto
    • Catania, CT, Italy
      • Ospedale Garibaldi
  • FG
    • San Giovanni Rotondo, FG, Italy
      • Ospedale Casa Sollievo della Sofferenza
  • GE
    • Genova, GE, Italy
      • Università degli Studi di Genova
  • MI
    • Milano, MI, Italy
      • IRCCS Ospedale Maggiore Policlinico
  • PE
    • Pescara, PE, Italy
      • Ospedale Civile Spirito Santo
  • RC
    • Reggio Calabria, RC, Italy, 89100
      • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
  • RM
    • Roma, RM, Italy
      • Ospedale Sant'Eugenio
    • Roma, RM, Italy
      • Policlinico Agostino Gemelli
    • Rome, RM, Italy
      • Azienda Ospedaliera Sant'Andrea
    • Rome, RM, Italy
      • IRCCS Istituto Regina Elena
  • SA
    • Salerno, SA, Italy
      • A.O.U. San Giovanni di Dio e Ruggi d'Aragona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 61 years or more
2. Newly diagnosed AML with > 30% myeloid marrow blasts, either "de novo" or evolving from a MDS not previously treated with chemotherapeutic agents.
3. Absence of central nervous system involvement

4. No contraindications for intensive chemotherapy, defined as:

   1. prior congestive heart failure requiring treatment and/or left ventricular systolic ejection fraction below the normal range;
   2. a creatinine or bilirubin level more than twice the upper limit of normal, except if AML-related;
   3. a Performance Status (PS) score of > 2;
   4. uncontrolled severe infection.
5. Informed consent.

Exclusion Criteria:

1. Age ≤ 60 years
2. Newly diagnosed AML with < 30% myeloid marrow blasts
3. Previously treated AML
4. Central nervous system involvement
5. Prior congestive heart failure requiring treatment and/or left ventricular systolic ejection fraction below the normal range;
6. A creatinine or bilirubin level more than twice the upper limit of normal, except if AML-related;
7. A PS score of > 2;
8. Uncontrolled severe infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azacitidine; Vidaza consists of 50 mg/ m2 s.c or i.v for 7 days (5 + weekend off + 2) every 28 days and increase after 1st cycle, if well tolerated, to 75 mg/m2 s.c or i.v. for 7 days (5 + weekend off + 2) every 28 days for further 5 cycles followed by cycles every 56 days for 4 years and six months	Drug: Vidaza 100 milligram (mg) injection; 1st cycle 50 mg/sqm s.c. or i.v. for 7 days (5 + weekend off + 2) every 28 days and increase dosing after 1st cycle, if well tolerated, to 75 mg/ m2 for further 5 cycles, followed by cycles every 56 days for 4 years and six months post-remission.; Other Names: Vidaza
Placebo Comparator: Best supportive care; No drug administration	Other: Best Supportive Care; Best supportive care includes antibiotics, transfusions and fluids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free Survival (DFS)	Disease-free survival (DFS) at 2 and 5 years. Events for DFS are death and first relapse (either AML or myelodysplastic syndrome (MDS) recurrence) and death; observations are censored at the date of last contact if alive and disease-free. DFS will be calculated from the date of achievement of CR to the date of 1st relapse or death. Patients still alive in 1st CR will be censored at the moment of last visit/contact.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalizations	Number and length of hospitalizations in the post-remission period.	5 years
Overall Survival (OS)	Overall survival (OS) at 2 and 5 years. Event for OS in both arms is death and patients are censored at the date of last contact if alive	2 and 5 years

Collaborators and Investigators

• Sponsor: Associazione Qol-one
• Investigators: Study Chair: Esther Natalie Oliva, QOL-ONE Associazione Culturale e di Ricerca

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2010
• Primary Completion (Actual): September 27, 2021
• Study Completion (Actual): September 27, 2021

Study Registration Dates

• First Submitted: December 27, 2021
• First Submitted That Met QC Criteria: December 27, 2021
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia,; Post-Remission Therapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: QOLESS-AZA-AMLE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No