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Treating leukaemia patients with chemotherapy and 2 repurposed drugs

Randomised phase II trial with safety run-in phase evaluating low-dose azacitidine, all-trans retinoic acid (ATRA) and pioglitazone versus standard dose azacitidine in patients ≥60 years of age with acute myeloid leukaemia (AML) who are refractory to standard induction chemotherapy (AML-ViVA).

Cancer types
Blood cancer
Trial phase


ACF funding
Estimated trial cost

Why this trial

Acute myeloid leukaemias (AML) are a group of heterogeneous disorders. Outcome is influenced by various factors, including patient features (e.g. age, other illnesses present) and disease characteristics. While responses can be achieved in 70-80% of younger adult patients with a 5-year survival rate of 40-45%, only about 40-60% of older patients achieve remission. The vast majority will relapse, with about 10% surviving more than 5 years.

For patients with AML that don’t respond to chemotherapy, the only option is stem cell transplantation. If no donor is available, or if the procedure is not feasible due to advanced age or other medical reasons, patients with this chemo-refractory AML have a median survival of only 62 days.

This number clearly demonstrates the need for effective treatment options in patients with refractory disease who are not eligible for stem cell transplantation.

Why this intervention

The most striking improvement in AML therapy has been achieved with all-trans retinoic acid (ATRA), which is a drug currently on the market for the treatment of acne. Several clinical trials have studied the role of ATRA in AML when given in combination with intensive chemotherapy. One study showed that the addition of ATRA to induction chemotherapy in AML patients >60 years of age resulted in a survival benefit.

Pioglitazone is currently on the market for the treatment of diabetes. Studies have shown that the drug is able to regulate cell growth and death. For AML specifically, preclinical data have demonstrated that PPARγ ligands (the drug group of pioglitazone) suppressed growth of AML cells, and, combined with ATRA, induced the development of normal cells instead of AML cells.

Azacitidine impacts cell differentiation, gene expression, and DNA synthesis and metabolism, and causes (tumour) cell death. Since the early 1970s, azacitidine continues to be investigated for the treatment of various types of leukaemia.

Taken together, it is reasonable and attractive to combine low-dose azacitidine, ATRA and pioglitazone in older patients with refractory AML to evaluate whether this combinatorial improves survival.

Trial design

The main trial was a randomised, phase II, open label, multi-centre trial in 76 adult patients with AML refractory to standard induction chemotherapy.

First, a safety run-in study was conducted with 10 patients receiving the study drugs azacitidine, all-trans retinoic acid (ATRA), and pioglitazone. Following this phase, data on toxicity and responses were analyzed to determine the appropriate doses for the main trial study. The main trial was planned to take place across 13 German centers.



The trial's first results were presented at the ASH conference in December 2019. It showed that the treatment is safe for this delicate patient population, with 3 out of 10 patients experiencing a complete response. Additionally, one patient saw their disease stabilize for 14 months.

The second part of the trial was supposed to compare the ViVA regimen to the standard dose of azacytidine. However, this part won't happen due to issues with the company providing azacytidine (and some funding) for the trial.

The investigators are now seeking alternative solutions to further explore the ViVA regimen in AML.

The full publication can be downloaded here.



  • Dr. Simone Thomas, University Hospital Regensburg, Regensburg, Germany (Coordinating Investigator)
  • Prof. A. Reichle, University Hospital Regensburg, Regensburg, Germany (Principal Investigator)


  • University Hospital Regensburg, Regensburg, Germany

Other partners:

  • Deutsch-Österreichische Studiengruppe Akute Myeloische Leukämie (AMLSG)

Our role

Financial support

Why we support this trial

Intervention has little or no commercial value

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Expected survival benefit

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No major hurdle for clinical implementation

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Benefits a population with high unmet needs

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ACF funding
Estimated trial cost

Questions about participation?

Simone Thomas
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Questions about this trial?

The Anticancer Fund
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More info on trial: NCT02942758

Hui, H., et al. (2014). Oroxylin A has therapeutic potential in acute myelogenous leukemia by dual effects targeting PPARγ and RXRα. Int J Cancer, 134, 1195-1206. doi:10.1002/ijc.28435

Schlenk, R.F., et al. (2016). All-trans retinoic acid as adjunct to intensive treatment in younger adult patients with acute myeloid leukemia: results of the randomized AMLSG 07-04 study. Annals of Hematology, 95(12), 1931–1942. doi:10.1007/s00277-016-2810-z

Nagel, G., et al. (2017). Epidemiological, genetic, and clinical characterization by age of newly diagnosed acute myeloid leukemia based on an academic population-based registry study (AMLSG BiO). Annals of Hematology, 96(12), 1993–2003.​ doi:10.1007/s00277-017-3150-3

Schlenk, R.F., et al. (2014). Phase III study of all-trans retinoic acid in previously untreated patients 61 years or older with acute myeloid leukemia. Leukemia, 18, 1798-1803. doi:10.1038/sj.leu.2403528

Tabe, Y., et al. (2012). Effects of PPARgamma Ligands on Leukemia. PPAR Research, 2012, 483656. doi:10.1155/2012/483656

Author: Kristine Beckers (Trial Manager)

Last updated: March 2024