BRUSSELS – The results of the AML-ViVA trial are available: low dose azacitidine, pioglitazone and all-trans retinoic acid is safe in 60+ Acute Myeloid Leukemia (AML) patients who do not respond to initial chemotherapy.

Patients with AML have very few treatment options when the initial chemotherapy has failed. This is particularly true for patients over 60, or with co-morbidities, who are not eligible for stem cell transplantation. On average, they will survive only a few months.

These dismal figures sadly demonstrate the need for effective treatment options in patients with refractory disease who are not eligible for stem cell transplantation. The AML-ViVA trial was initiated, thanks to the financial support of the Anticancer Fund, to address this problem.

10 patients were treated in 5 hospitals

In the first stage of AML-ViVA, which has recently been reported in a scientific article, 10 patients ≥60 years of age with AML not responding to chemotherapy and not eligible for stem cell transplantation were included between May 2017 and March 2020. These 10 patients were treated in 5 hospitals of the German-Austrian AML study group (AMLSG) in Germany. The aim of this first stage was to evaluate the safety and confirm the appropriate dose of the combination of azacitidine, all-trans retinoic acid, and pioglitazone, coined the ViVA treatment. Next to the Anticancer Fund who provided 50% of the funding, the company making azacitidine, Celgene, funded the other 50% and kindly provided the drug azacitidine.

All-trans retinoic acid is a drug used to treat another type of leukaemia. Pioglitazone is used for the treatment of diabetes. Azacitidine is already used in some AML patients but does not provide a long-lasting effect as a single drug. Based on preliminary results in patients and work done in the lab, the combination was expected to help AML patients by inducing differentiation, making the leukaemia cells revert to normal hematologic cells.

Dr. Gauthier Bouche, director of Clinical Research of the Anticancer Fund says: “We were enthused by the quality of the published data that included observations in 5 patients treated compassionately with the ViVA treatment. Jointly funding the trial with the company making azacitidine was also a plus, as it showed interest from the company, at least initially, in the ViVA regimen as well.”

Results confirmed treatment is well tolerated

The results have been very informative and encouraging. They confirmed that the ViVA treatment is well tolerated and that it does induce differentiation, as anticipated, in patients whose leukaemia improved thanks to the ViVA treatment. In 4 of the 10 patients treated, the leukaemia regressed with 3 patients experiencing a complete remission and one patient having a partial remission.

However, to draw any conclusions on the efficacy of the trial treatment, a larger number of patients were needed. This was the initial plan of the AML-ViVA trial, which was designed to evolve into a multicentred, prospective, open-label, randomised phase II trial. Due to slow recruitment the investigators decided to stop after completion of the safety run-in part.

The treatment of AML patients who are refractory to chemotherapy has changed since 2017 with a few other options now available. The ViVA treatment represents an interesting option to be studied further in this new context.

“For patients who did not respond to induction chemotherapy the prognosis is still dismal. These patients suffer often from severe neutropenia and consecutive infections representing the major cause of death. Thus, we were really intrigued to observe differentiation of leukemic blasts in the AML-ViVA trial: induction of differentiation, the holy grail in AML therapy, reduces leukemic cell counts while improving immunity. Given the very tolerable safety profile and the encouraging efficacy the AML-ViVA treatment warrants further clinical investigation and represents also a very promising backbone for combination therapies with novel innovative drugs” says Dr. Daniel Heudobler of the University Hospital Regensburg, and first author of the publication.

Find out more about the AML-ViVA trial here.