Clinical Trial: SC-PEG Asparaginase vs. Oncaspar in Pediatric Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized Study of Intravenous Calaspargase Pegol (SC-PEG Asparaginase) and Intravenous Oncaspar in Children and Adolescents With Acute Lymphoblastic Leukemia or Lymphoblastic L

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 tr

Detailed Summary:

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) durin
Sponsor: Dana-Farber Cancer Institute

Current Primary Outcome:

  • Asparaginase-related toxicity [ Time Frame: 2 years ]
    Number of participants with adverse events related to asparaginase, including pancreatitis, thrombosis and hypersensitivity reactions
  • Asparaginase pharmacokinetics [ Time Frame: 2 years ]
    Serum asparaginase activity levels and asparaginase antibody levels, assayed immediately after 1st dose, then 4,11,18,and 25 days after 1st dose, and then prior to every dose of asparaginase given during post-induction phases of treatment.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Frequency of Infections [ Time Frame: 2 years ]
    Number of episodes of bacteremia, fungemia and invasive fungal infections during the remission induction phase
  • Outcome [ Time Frame: 2 years ]
    Rates of complete remission, relapse, induction death, remission death, and second malignant neoplasms in participants
  • Outcome of participants with very-high risk disease [ Time Frame: 2 years ]
    Rates of relapse, remission death and second malignant neoplasm in participants with high MRD and/or high risk cytogenetics who are treated with a more intensified regimen
  • Feasibility of Vitamin D Screening/Supplementation [ Time Frame: 2 years ]
    Vitamin D-levels at various times during treatment, proportion of participants with low vitamin D levels, proportion of participants who agree to Vitamin D supplementation
  • Feasibility of prospective screening for ABGD [ Time Frame: 2 years ]
    Number of samples from participants with T-ALL in which a successful result was obtained by qPCR to assess absence of biallelic TCRy deletions (ABGD); frequency of ABGD in T-ALL
  • Feasibility of prospective screening for genetic abnormalities [ Time Frame: 2 years ]
    Number of samples from participants with B-ALL in which a successful result was obtained in prospective screening for abnormalities (eg, mutations, deletions, rearrangements) of IKZF1, CRLF2 and JAK1/2 in patients with newly diagnosed B-ALL; proportion of participants with B-ALL found to have one of these abnormlaties.
  • Relationship Between Apoptotic/Anti-apoptotic proteins and Response to CT [ Time Frame: 2 years ]
    Levels of pro- and anti-apoptotic proteins in participant samples from diagnosis; correlation of these levels to clinical response (induction failure, high MRD, relapse).


Original Secondary Outcome: Same as current

Information By: Dana-Farber Cancer Institute

Dates:
Date Received: April 5, 2012
Date Started: April 2012
Date Completion: June 2017
Last Updated: August 1, 2016
Last Verified: August 2016