Patients

Why is the trial being conducted?

We founded the RESOLVE consortium (Residual disease assessment in hematologic malignancies to improve patient-relevant outcomes across Europe) to better understand the role of MRD for personalized treatment decisions. The trial investigates whether treatment intensity can be safely reduced in MRD negative patients after an initial treatment, and thereby reduce side effects and economic burden, and increase patients’ quality of life.

Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is a type of cancer that affects early forms of blood cells. These abnormal blood cells grow rapidly, accumulate in the bone marrow, and disrupt the normal production of blood cells. Low levels of blood cells increase the risk of infections, cause anemia leading to fatigue, and result in a condition called thrombocytopenia, which raises the chances of bleeding. Infections are the main cause of death in people with AML, while a smaller number of patients may experience fatal bleeding events. AML is the most common form of acute leukemia in adults. Current treatment strategies comprise of induction and consolidation chemotherapy and may also include allogeneic hematopoietic cell transplantation.

While induction therapy should induce an initial response, consolidation therapy has the intention of preventing disease progression or relapse. Current consolidation therapies can have side effects and may impact the patient’s quality of life. The choice of therapies and their intensities for a patient is dependent on age, comorbidities, nature of AML and other factors. Recent evidence has suggested, that certain AML patients with specific disease characteristics might not need the most intense treatment currently available, allogeneic hematopoietic cell transplantation. Therefore, it would help to identify those patients beforehand and reduce their treatment intensity accordingly.

Current treatment guidelines for acute leukemias suggest the quantification of residual disease (measurable residual disease, or MRD) by a technology called flow cytometry, for this identification approach. Measurable residual disease describes the presence of a very small number of leukemia cells in the body after a treatment that cannot be detected by conventional diagnostic tests, but may influence relapse risk. While flow cytometry is already widely utilized in leukemia diagnosis and subtype differentiation, as well as therapeutic decision-making for some leukemia subtypes, there is still a debate about how flow-cytometry-assessed MRD results can be used to guide treatment decisions in patients with AML. Mounting evidence suggests that ELN intermediate risk AML patients with a negative MRD result – those with residual disease below a certain detection limit following initial treatment – may be at a lower risk of relapse. We therefore hypothesize that treatment intensity can be safely reduced in those patients, with chemotherapy instead of allogeneic transplantation, and thereby reduce their side effects, economic burden, and increase their quality of life. This trial will prove the effectiveness of reducing treatment intensity in MRD-negative AML patients with intermediate risk disease in a real-world setting with our main objective being to show that overall survival with chemotherapy will be comparable to overall survival with allogeneic transplantation.

Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SSL) are a type of blood cancer that affects cells of the lymphatic system. In CLL/SLL, an immune cell undergoes malignant changes and divides uncontrollably.. CLL/SLL is the most prevalent form of adult leukemia in the Western world, typically appearing around the age of 72 and affecting more than 41,000 individuals annually in Europe. At the time of diagnosis only a minority of patients with CLL require treatment, but the need for treatment may occur over the following years. Thus, patients with CLL receive life-long monitoring. When the disease progresses with for example enlarged lymph nodes, anemia, low platelet values, or an enlarged spleen, current treatment guidelines recommend targeted therapies with so called BTK inhibitors (BTKi), BCL2 inhibitors (BCL2i), and anti-CD20 monoclonal antibodies (MoAb).

BTK inhibitors work like a lock and key, blocking signals that help leukemia cells grow. BCL2 inhibitors help by stopping a protein that helps leukemia cells survive, making it easier for the body to fight the disease. Anti-CD20 monoclonal antibodies act by tagging the leukemia cells, helping the immune system find and attack them more easily. These medicines are part of newer and effective treatments for CLL/SLL. They are generally safe, but still carry the risk of various significant side effects, including diarrhea, fatigue, infections, bleeding, cardiovascular complications and others. Besides impacting the patient’s quality of life they also pose a financial burden on the health system.

The disease showcases a highly varied clinical journey—some patients may never need treatment, while others encounter an aggressive form of the disease with frequent relapses. Patients meeting specific criteria indicating progression require treatment, while asymptomatic patients with low disease burden are usually observed following a watch-and-wait approach.

Available treatments may be administered continuously until disease progression or unacceptable toxicity (like BTKi monotherapy) or for fixed duration (like the combination of BCL2i+anti-CD20 MoAb or BCL2i+BTKi). Current treatment guidelines for leukemias suggest the quantification of residual disease (measurable residual disease, or MRD) for fixed-duration approaches. Measurable residual disease describes the presence of a very small number of leukemia cells in the body after a treatment that cannot be detected by conventional diagnostic tests, but may influence relapse risk. While MRD is already widely utilized in leukemia diagnosis and subtype differentiation, as well as therapeutic decision-making for some leukemia subtypes, there is still a debate about how MRD results can be used to guide treatment decisions in patients with CLL/SLL. Mounting evidence suggests that patients with CLL/SLL and undetectable MRD (uMRD)– those with residual disease below a certain detection threshold following initial treatment – may be at a lower risk for relapse, even without prolonged therapy. The RESOLVE trial will evaluate whether a shorter duration of treatment in patients without residual disease (MRD negative) have a lower burden of side effects with the same efficacy.

If you are interested in participating please contact a trial site close to you.

Patients

Why is the trial being conducted?

Acute Myeloid Leukemia

Chronic Lymphocytic Leukemia

Participating Trial Sites

Acute Myeloid Leukemia

Chronic Lymphocytic Leukemia