Personalized therapies for leukemia: Clinical trial from Dresden and Kiel investigates innovative medication after stem cell transplantation

Acute myeloid leukemia (AML) is an aggressive form of blood cancer that carries a high risk of relapse even after stem cell transplantation. The PIVOT clinical trial, which has now been launched by scientists from Dresden and Kiel, is investigating whether the drug Ivosidenib can help to reduce the risk of relapse and improve patients' chances of survival. The drug Ivosidenib was approved in Europe in 2023 for the treatment of diseases including AML. Ivosidenib has shown to lead to a better treatment response particularly in patients with an IDH1 mutation. The focus of the PIVOT clinical trial is on long-term survival.

Acute myeloid leukemia is characterized by specific gene mutations. One of the most common mutations affects the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2. IDH1 mutations can be detected in approximately six to eight percent of adult AML patients. In Germany, about 400 individuals develop blood cancer with this mutation each year. Despite allogeneic stem cell transplantation, the risk of relapse is high. Ivosidenib, an IDH1 inhibitor, could reduce the likelihood of molecular relapse and improve long-term survival.

“The PIVOT study is of major importance for science and clinical research because it will provide new insights into the maintenance therapy with Ivosidenib following stem cell transplantation and could potentially revolutionize the treatment for IDH1-mutated AML,” explains Dr. Jan Middeke, senior physician at the Medical Clinic I of the University Hospital Dresden and one of the two principal investigators. “For the affected patients, this opens up the possibility of reducing the risk of relapse and achieving a longer, disease-free life. 

Co-principal investigator Prof. Friedrich Stölzel, Head of the Division of Stem Cell Transplantation and Cellular Immunotherapy at the Department of Internal Medicine II, University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, and Professor of Stem Cell Transplantation and Cellular Immunotherapy at the Faculty of Medicine at Kiel University (CAU), adds: “This project is a significant step in the development of more precise and individualized therapies that are tailored to the genetic makeup of the tumor. In the long term, the clinical trial could open up new treatment options for other patient groups and thus continue to improve the chances of recovery for leukemia patients.”

“This form of personalized cancer therapy is one of the three main research areas of University Medicine in Dresden,” explains Prof. Esther Troost, Dean of the Faculty of Medicine at TU Dresden. “We are proud to be able to conduct this study at the National Center for Tumor Diseases Dresden (NCT/UCC) and to collaborate with our colleagues in Kiel.” “Such challenging clinical trial concepts can only be implemented within large national network projects involving high-performing medical faculties and university hospitals,” Prof. Claudia Baldus, Vice-Dean of the Faculty of Medicine at Kiel University and board member of the University Cancer Center Schleswig-Holstein (UCCSH), explains.

Patients participating in the clinical trial will receive daily maintenance treatment with Ivosidenib over two years, while being closely monitored by a medical team. Key objectives are to increase the survival rate, to achieve the disappearance of detectable leukemia cells, and to monitor for side effects.

“If this therapy proves successful after the two-year testing phase, it could become a new standard for patients with an IDH1 mutation after stem cell transplantation, “ Jan Middeke and Friedrich Stölzel are convinced. 

Clinical trial and trial design:
The PIVOT study is substantially supported by the Study Alliance Leukemia (SAL) and the AML Cooperative Group (AMLCG), as well as the Cooperative Transplant Group (KTS). The SAL, the AMLCG, and the KTS are leading research networks that investigate innovative therapeutic approaches for the treatment of leukemias in order to improve the chances of patient recovery. The clinical trial is sponsored by Servier Germany, TU Dresden and SAL.

The PIVOT clinical trial has a multi-stage design:

• Screening phase: Enrollment of patients within 100 days of transplantation
• Treatment phase: Daily administration of Ivosidenib for 24 months
• Follow-up phase: Survival and safety monitoring for up to five years after the end of the therapy

Patient selection and safety aspects:
Eligible patients must be adults aged 18 years or older with confirmed IDH1-mutated AML or MDS after transplantation. Strict inclusion and exclusion criteria ensure patient safety. The clinical trial is being conducted at several university hospitals and oncology centers in Germany.

Scientific directors and contact:
Dr. Jan Moritz Middeke (University Hospital Dresden) and Prof. Friedrich Stölzel (University Hospital Schleswig-Holstein) are the medical directors of the clinical trial.

More information: www.aml-germany.com
Participation: pivot@ukdd.de

Contact: 
Dr. Jan Moritz Middeke
Carl Gustav Carus University Hospital Dresden
Medical Clinic and Policlinic I
JanMoritz.Middeke@ukdd.de

Prof. Friedrich Stölzel
University Hospital Schleswig-Holstein, Campus Kiel
Medical Clinic II, Division of Stem Cell Transplantation and Cellular Immunotherapy
Friedrich.stoelzel@uksh.de