SC-PEG Asparaginase vs. Oncaspar in Pediatric Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma
Condition: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin
Intervention: SC-PEG; Oncaspar
Intervention description: 11 doses Intravenously over one hour; 16 doses Intravenously over one hour
Intervention MeSH terms: Pegaspargase
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 240.0
Sex: All
Minimum age: 365 Days
Maximum age: 21 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed diagnosis of ALL or lymphoblastic leukemia

          -  No prior therapy except short courses of corticosteroids, a single dose of IT
             cytarabine or emergent radiation to the mediastinum or other life-threatening masses

        Exclusion Criteria:

          -  Have received more than 7 days of corticosteroids in the preceding 4 weeks or more
             than 28 days of corticosteroids in the preceding 6 months

          -  Have received any chemotherapy or radiotherapy for previous malignancy

          -  Receiving any other investigational agent

          -  Known to be HIV positive

          -  Uncontrolled intercurrent illness

          -  Pregnant or breastfeeding

          -  History of previous malignancy