SC-PEG Asparaginase vs. Oncaspar in Pediatric Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma
brief summary
This study is being conducted to learn about the effects of SC-PEG, which is a new form of a chemotherapy drug called asparaginase. Asparaginase is used to treat ALL and lymphoblastic lymphoma. The standard form of asparaginase, called Elspar, is given in the muscle once a week for 30 weeks. There are other forms of asparaginase. The investigators will be studying two of these: Oncaspar and Calaspargase Pegol (SC-PEG). The investigators have previously studied giving Oncaspar in the vein (instead of the muscle) every 2 weeks in patients with ALL, and have shown that this dosing did not lead to any more side effects than Elspar given weekly in the muscle. The study drug, SC-PEG, is very similar but not identical to Oncaspar. SC-PEG has been given in the vein to children and adolescents with ALL as part of other research studies, and it appears to last longer in the blood after a dose than Oncaspar. It has not yet been approved by the FDA. The goal of this research study is to learn whether the side effects and drug levels of SC-PEG given in the vein every 3 weeks are similar to Oncaspar given into the vein about every 2 weeks. The study will also help to determine whether changing treatment for children and adolescents with ALL with high levels of minimal residual disease may improve cure rates. Measuring minimal disease (MRD) is a laboratory test that finds low levels of leukemia cells that the investigators cannot see under the microscope. In the past, it has been shown that children and adolescents with ALL with high levels of MRD after one month of treatment are less likely to be cured than those with low levels of MRD. Therefore, on the study, the bone marrow and blood at the end of the first month of treatment will be measured in participants with leukemia, and changes in therapy will be implemented based on this measurement. It is not known for sure that changing treatment will improve cure rates. MRD levels can only be measured if the marrow is filled with cancer cells at the time of diagnosis. Therefore, MRD studies will only be done in children and adolescents with ALL and not in those with lymphoblastic lymphoma. Another part of the study is to determine whether giving antibiotics during the first month of treatment even to participants without fever will prevent serious infections in the blood and other parts of the body. About 25% of children and adolescents with ALL and lymphoblastic lymphoma who receive standard treatment develop a serious blood infection from a bacteria during the first month of treatment. Typically, antibiotics (medicines that fight bacteria) are given by vein only after a child with leukemia or lymphoma develops a fever or have other signs of infection. In this study, antibiotics will be given by mouth or in the vein to all participants during the first month of treatment, whether or not they develop fever. Another goal of the study to learn how vitamin D levels relate to bone problems (such as broken bones or fractures) that children and adolescents with ALL and lymphoblastic lymphoma experience while on treatment. Some of the chemotherapy drugs used to treat ALL and lymphoblastic lymphoma can make bones weaker, which make fractures more likely. Vitamin D is a natural substance from food and sunlight that can help keep bones strong. The investigators will study how often participants have low levels of vitamin D while receiving chemotherapy, and, for those with low levels, whether giving vitamin D supplements will increase those levels. Another focus of the study is to learn more about the biology of ALL and lymphoblastic lymphoma by doing research on blood, bone and spinal fluid bone marrow samples. The goal of this research is to improve treatment for children with leukemia in the future.
detailed description
To determine whether or not children and adolescents with ALL or lymphoblastic lymphoma are eligible to participate in this study, screening tests will be performed, which may include the following: medical history, bone marrow tests, assessment of your tumor, blood tests and/or an EKG.
Participants who enroll in this study will receive with anti-leukemia drugs called chemotherapy. During study treatment, the study doctors will continue to perform tests on blood, bone marrow and spinal fluid to assess how the disease is responding to the study treatment and to look for possible side effects. Scans (for example, x-ray, CT scan or MRI scan) may also be done after beginning study treatment to look for possible side effects. If the disease was initially diagnosed by a scan, it will also be repeated during the study treatment to assess how it is responding.
There are three different treatment groups in which leukemia and lymphoblastic lymphoma can be divided and they differ slightly in the types and amounts of chemotherapy drugs used during the 2-years of therapy. Participants are assigned to the different categories based on the features of their leukemia or lymphoma, such as their age, white blood cell count, and results of other tests. The three different treatment groups are called "Standard Risk", "High Risk" and "Very High Risk".
Participants will be given several different chemotherapy drugs during many periods of treatment (called "phases"). These drugs are known to kill lymphoblastic cancer cells. Some of the drugs are given by mouth, some into the veins (intravenously), and others as an injection (a shot) into the muscle. Some chemotherapy drugs will be given directly into your spinal fluid (called intrathecal chemotherapy) during a lumbar puncture (spinal tap). This treatment helps prevent the cancer cells from coming back in the spinal fluid and brain.
The first phase of treatment is steroid prophase. This phase of treatment is typically given in the hospital. This phase of treatment will begin immediately.
after enrolling on the study.
The second phase of treatment is remission induction. This phase will begin immediately after the steroid prophase and will last four weeks. Participants typically remain in the hospital for most (sometimes all) of this phase.
At the end of the remission induction phase, participants will undergo tests to determine if they are in remission. This testing will involve getting samples of blood, bone marrow and spinal fluid to look for cancer cells under the microscope. This testing will also involve getting repeat scans if these were not normal at the time of diagnosis. Remission means that cancer cells cannot be detected under the microscope in the blood, marrow and spinal fluid, and that any cancer previously seen on a scan has significantly improved or is no longer seen. Participants must be in remission to go onto the next phases of treatment; alternative treatments will be discussed with participants who are not in remission at the end of the induction phase.
official title
Randomized Study of Intravenous Calaspargase Pegol (SC-PEG Asparaginase) and Intravenous Oncaspar in Children and Adolescents With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma