Clinical trial NCT04454580: Hypomethylating Agents and Venetoclax in Newly Diagnosed Acute Myeloid Leukemia Patients Not Eligible for Intensive Chemotherapy
Official title: Retrospective, Observational, Monocentric Study to Assess Efficacy and Safety of the Combination of an Hypomethylating Agent in Combination With Venetoclax for Newly Diagnosed Acute Myeloid Leukemia Patients Not Eligible for Intensive Chemotherapy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Myeloid Leukemia, Adult
Hypomethylating Agents
Venetoclax
Lead sponsor: Ospedale Maggiore Di Trieste
Sponsor class: OTHER
First posted: 2020-07-01
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population includes adult patients with newly diagnosed acute myeloid leukemia not eligible for intensive chemotherapy, treated in a referral center for hematology

Brief summary: This is a retrospective, observational, monocentric study to evaluate the efficacy and safety of the combination of an hypomethylating agent with venetoclax newly diagnosed patients with acute myeloid leukemia ineligible for intensive chemotherapy

Detailed description: The prognosis of acute myeloid leukemia (AML) patients who are ineligible for intensive chemotherapy is poor (Kantarjian et al). Hypomethylating agents, azacitidine and decitabine, are effective and less toxic regimens, and treatment with these agents has improved the prognosis of these patients (Fenaux et al).

Venetoclax, a Bcl-2 inhibitor, in combination with azacitidine has shown efficacy in AML patients with complete remission rate of 73% and overall survival at 2 years of 40-50% (Di Nardo et al).

On these grounds, the aim of this study is to collect the real-life experience with this combination in previously untreated AML patients.

Eligibility criteria: Inclusion Criteria:

* age ≥18 years
* newly diagnosed acute myeloid leukemia not eligible for intensive chemotherapy

Exclusion Criteria:

* promyelocytic acute myeloid leukemia
* patients who have already received one or more prior lines of therapy

Primary outcomes:
measure: Complete response (CR) rate
timeFrame: every three months after started treatment up to two years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: every three months after started treatment up to two years
measure: Morphologic leukemia-free state (MLFS)
timeFrame: every three months after started treatment up to two years
measure: Progression-free-survival
timeFrame: from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 2 years
measure: Overall survival
timeFrame: from the start of the treatment until the date of documented progression or date of death from any cause, assessed up to 2 years
measure: adverse events and serious adverse events
timeFrame: through study completion, for an average of 1 year
Other outcomes:
Locations:
city: Trieste
country: Italy
facility: SC Ematologia Ospedale Maggiore
Study officials:
affiliation: SC Ematologia Ospedale Maggiore Trieste
name: Francesco Zaja, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Gattermann N, Germing U, Sanz G, List AF, Gore S, Seymour JF, Dombret H, Backstrom J, Zimmerman L, McKenzie D, Beach CL, Silverman LR. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010 Feb 1;28(4):562-9. doi: 10.1200/JCO.2009.23.8329. Epub 2009 Dec 21.
citation: DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, Frankfurt O, Konopleva M, Wei AH, Kantarjian HM, Xu T, Hong WJ, Chyla B, Potluri J, Pollyea DA, Letai A. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019 Jan 3;133(1):7-17. doi: 10.1182/blood-2018-08-868752. Epub 2018 Oct 25.
citation: Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Lowenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28.
citation: Kantarjian H, Ravandi F, O'Brien S, Cortes J, Faderl S, Garcia-Manero G, Jabbour E, Wierda W, Kadia T, Pierce S, Shan J, Keating M, Freireich EJ. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010 Nov 25;116(22):4422-9. doi: 10.1182/blood-2010-03-276485. Epub 2010 Jul 28.