A Study of Tailored Treatment Strategies for Patients with Acute Myeloid Leukemia or Chronic Lymphocytic Leukemia Without Detectable Residual Disease

Acute myeloid leukemia (AML) is a malignant disease of the hematopoietic system in which immature precursor cells multiply uncontrollably in the bone marrow and displace normal blood cell production. The standard initial treatment is chemotherapy, which is usually continued with additional cycles to stabilize the disease and kill any remaining cancer cells. Subsequently, patients with a moderate to high risk of relapse may undergo an allogeneic (from a donor) stem cell transplant, in which patients receive blood-forming cells from donors. Even after seemingly successful treatment, individual cancer cells may remain that are detectable only through specialized methods (minimal/measurable residual disease, MRD). If no residual cancer cells are detectable (MRD-negative), this is associated with a significantly lower risk of relapse and thus a better prognosis. However, a relapse remains possible. Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers in which abnormal B lymphocytes (a type of white blood cell that produces antibodies for immune defense) accumulate in the blood, bone marrow, and lymph nodes. As initial treatment, patients receive a fixed-duration regimen of venetoclax combined with obinutuzumab or with ibrutinib. Venetoclax inhibits a protein (BCL-2) that protects leukemia cells from programmed cell death, thereby allowing this process to be reactivated. Obinutuzumab is an antibody that binds to B cells and is intended to trigger their destruction. Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that blocks the survival and growth signals of CLL cells.

The goal of the present RESOLVE study is to compare standard treatment with reduced-intensity therapy in MRD-negative patients with AML and CLL/SLL. The study is open-label, meaning that patients and study physicians know which treatment is being administered. After enrollment in an MRD registry, MRD-negative patients are randomly assigned to one of two treatment groups within their study arm (Arm A: AML, Arm B: CLL/SLL) are randomly assigned to one of two treatment groups. In Arm A, Group 1 receives a standard preparatory treatment followed by an allogeneic stem cell transplant to consolidate the therapeutic success. In addition, medications may be used to prevent what is known as graft-versus-host disease. This is a potential complication of stem cell transplantation in which the donor’s foreign immune cells attack the recipient’s healthy cells. Group 2, on the other hand, does not receive an immediate allogeneic stem cell transplant; instead, consolidation chemotherapy is administered first. A later stem cell transplant, depending on the course of MRD, remains a possibility. The goal is to investigate whether an allogeneic stem cell transplant can be omitted without compromising overall survival (OS). In Arm B, Group 3 continues standard initial treatment. In Group 4, treatment is discontinued after the second confirmed MRD-negative result. The goal is to investigate whether treatment can be discontinued earlier once undetectable MRD is achieved, thereby reducing the burden of side effects.

Eligible participants for Arm A are patients aged 18 to 70 with newly diagnosed intermediate-risk AML who are MRD-negative after one to two cycles of chemotherapy and are suitable candidates for a stem cell transplant. In Arm B, patients aged 65 and older with CLL or SLL who were MRD-negative twice in a row during their initial treatment are eligible to participate. Certain subtypes of AML, as well as relapsed or refractory CLL, exclude patients from participation.