A Study of the Combination of the Chemotherapeutic Agents Vyxeos® (liposomal daunorubicin and cytarabine) and Clofarabine in Children with Relapsed or Treatment-Resistant Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a form of blood cancer characterized by the uncontrolled proliferation of immature white blood cells in the bone marrow. For children and adolescents whose AML returns (relapses) after initial treatment or does not respond to standard therapy (refractory), treatment options are limited. This often happens because treatment usually cannot completely destroy all cancer cells. Particularly resistant leukemia cells can remain in the body, remain dormant for an extended period, and later begin to multiply again. In addition, the leukemia cells can undergo genetic changes over time, making them resistant to therapy. The immune system, which normally plays an important role in controlling cancer cells, is often weakened by the disease or treatment and cannot adequately fight off any remaining leukemia cells. In such cases, patients typically receive combination therapy consisting of the drugs fludarabine, cytarabine, and daunorubicin, followed by further chemotherapy and a stem cell transplant. The combination of cytarabine and daunorubicin has proven effective, but there is a desire to find better alternatives, particularly for daunorubicin. This is especially true for young patients, for whom certain side effects—such as heart damage—can be severe in the long term. The drug Vyxeos® offers a potential alternative. It combines these two well-established chemotherapy drugs, daunorubicin and cytarabine. What makes it unique is the way these two substances are administered: they are enclosed in tiny fat droplets called liposomes. These lipid capsules ensure that the active ingredients are delivered more precisely into the body, break down more slowly, and remain in the bloodstream longer. As a result, the medication can penetrate cancer cells more effectively and take effect there. At the same time, healthy tissue in the body is subjected to less stress, leading to fewer side effects. This special formulation is therefore designed to increase the effectiveness of chemotherapy while improving tolerability for patients. Clofarabine is administered concurrently; this medication is intended to enhance the effectiveness of Vyxeos® by supporting the action of the cytarabine it contains. It ensures that more of the active form of cytarabine (Ara-CTP) is produced. As a result, more of the active ingredient accumulates in the cells, which kills the cancer cells more effectively. Vyxeos® is already approved for the treatment of certain types of AML in adult patients. The goal of the VyClo study is to test the combination of Vyxeos® and clofarabine together for the first time in children and adolescents with relapsed or refractory AML, in order to determine the optimal dosage of this combination and evaluate its safety. All participating children and adolescents will receive the same treatment. It will be administered through a vein (intravenously), and patients will be closely monitored to detect any potential side effects early on. Participation in the study involves two consecutive treatment cycles. In the first cycle, patients receive the study drug Vyxeos® on days 1, 3, and 5. In addition, clofarabine is administered from day 2 through day 6. This first cycle is followed by a rest period. The length of this break may vary from person to person, but is typically about 4 weeks. During this time, patients are closely monitored by medical staff. This is followed by the second cycle, during which Vyxeos® is administered again on days 1, 3, and 5—but this time without clofarabine. The total duration of the study depends on how well the treatment is tolerated and how the disease progresses. Children, adolescents, and young adults aged at least one year through 21 years who have experienced a relapse of acute myeloid leukemia (AML) are eligible to participate. Eligibility applies after the second relapse or in the case of a very early first relapse—that is, when the disease has recurred within one year of the initial diagnosis. Patients with so-called refractory AML—meaning that the leukemia has not responded sufficiently to standard chemotherapy and leukemia cells are still detectable in the bone marrow—are also eligible to participate. Participation may also be considered for patients with certain high-risk characteristics. In addition, patients must be in sufficiently good general health, as measured by the Lansky score (for children under 16 years of age) or the Karnofsky score (for adolescents 16 years of age and older); this score must be at least 60 in each case. Pregnancy or breastfeeding excludes participation. No other cancer medications may be taken during the study unless they are expressly permitted.