SC-PEG Asparaginase vs. Oncaspar in Pediatric Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma
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.
|Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma||Drug: SC-PEG Drug: Oncaspar||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|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|
- 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.
- 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).
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||July 2017|
|Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Active Comparator: SC-PEG
11 doses Intravenously over one hour
Active Comparator: Oncaspar
16 doses Intravenously over one hour
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01574274
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02215|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian|
|New York, New York, United States, 10032|
|Montefiore Medical Center|
|New York, New York, United States, 10467|
|United States, Rhode Island|
|Hasbro Children's Hospital|
|Providence, Rhode Island, United States, 02903|
|United States, Virginia|
|INOVA Fairfax Hospital|
|Falls Church, Virginia, United States, 22042|
|Hamilton, Ontario, Canada|
|Hospital Sainte Justine, University of Montreal|
|Montreal, Quebec, Canada|
|Centre Hospitalier U. de Quebec|
|Quebec City, Quebec, Canada|
|San Jorge Children's Hospital|
|San Juan, Puerto Rico|