Randomized Study of Intravenous Calaspargase Pegol (SC-PEG Asparaginase) and Intravenous Oncaspar in Children and Adolescents With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
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
The Consolidation I phase begins once it is determined that a participant is in remission.
This phase lasts about three weeks. This phase of treatment is given in the hospital, but
participants may be able to leave the hospital after the first week of the phase. The
purpose of this phase is to further reduce the number of cancer cells in the body.
The next phase is the Central Nervous System (CNS) phase, and is usually given in the
outpatient setting. Participants may need to be admitted to the hospital during this phase
of treatment if a complication develops, such as infection. This phase of therapy begins
immediately after the Consolidation I phase and lasts about 3 weeks. Treatment involves a
series of lumbar punctures with anti-leukemia drugs given intrathecally over a two week
period. Anti-leukemia drugs will also be given by mouth and by vein during this phase as
well. Some participants may receive radiation therapy during this phase, although most do
not. The decision to treat with radiation or not is based on characteristics of the cancer
at diagnosis and whether or not cancer cells were seen in spinal fluid at that time.
Radiation therapy is a painless procedure, the purpose of which is to prevent leukemia from
coming back in the brain. For participants who receive radiation therapy, it will be given
in either 8 or 10 daily treatments, depending on how many leukemia cells were seen in the
spinal fluid under the microscope at diagnosis.
The next phase of the study is Consolidation II. This phase begins about 3 weeks after
starting the CNS phase and lasts for about 27 weeks. During this phase, chemotherapy is
given in three-week cycles, with some drugs given in clinic and some drugs given by mouth at
home. Participants are typically treated as outpatients during this phase.
The last phase is called Continuation. This is also usually given as an outpatient. The goal
of this phase is to rid the body of all remaining cancer cells. The cycles of chemotherapy
during this phase are repeated every 3 weeks, with some drugs given in clinic and some drugs
given by mouth at home. This phase will ends two years after remission was documented.
The randomization in this study involves the two forms of asparaginase, Oncaspar and SC-PEG
asparaginase. Because no one knows which of the study options is best, participants will be
"randomized" into one of the study groups: to receive Oncaspar or to receive SC-PEG.
Randomization means that participants are put into a group by chance. Participants who are
placed in the Oncaspar group will receive a single dose of Oncaspar on Day 7 of the
Remission Induction phase, and then every 2 weeks for 30 weeks starting in the CNS phase (16
total doses of Oncaspar). Participants placed in the SC-PEG group will receive SC-PEG
asparaginase on Day 7 of the remission induction phase and then every 3 weeks beginning in
the CNS phase (11 total doses of SC-PEG).
Minimal Residual Disease (MRD) testing is a way to look for very low levels of leukemia in
the body that cannot be seen under the microscope. These test will be done in a laboratory
at Dana-Farber Cancer Institute. If the MRD results are in the low range on Day 32, thre
will be no change to the treatment program described above. If the MRD results are in the
high range, then it will be recommended that treatment be changed.
Participants will receive a fluoroquinolone antibiotic beginning during the first phase of
treatment and continuing until the neutrophils and monocytes (two types of white blood cells
in the blood that help fight infection) have increased. The goal of giving the antibiotics
is to prevent infection during the first few weeks of treatment.
Participants who agree to have extra blood drawn to test for vitamin D levels in the blood
will have 1 teaspoon of blood drawn at the following times: start of treatment, at the end
of the first month of treatment, at the start of the continuation phase, and at the end of
treatment. Participants will receive the results of these tests. If the vitamin D level is
low, the study doctor will recommend that the participant take a vitamin D supplement.
Participants may choose not to have blood drawn to check vitamin D levels, or may choose not
to take the vitamin D supplement.
Participants will be asked at the time of study entry if they agree to provide additional
blood and bone marrow samples for research. These additional samples will be used to learn
more about the biology of ALL and lymphoblastic lymphoma. Stored specimens may also be used
for future research regarding leukemia.
After completing all treatment, participants will be asked to come in for physical exams and
blood work every month for the first six months after the final treatment, then every two
months for the next 6 months, then every four months for the next year, and then every six
months for the next year. After that we will ask you to come in once a year.
The investigators would like to keep track of the medical condition of all participants for
the rest of their lives. This will be done by reviewing medical records of participants.
The investigators may telephone participants who have finished treatment to see how they are
doing if they have not been seen by their doctor for at least a year.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of participants with adverse events related to asparaginase, including pancreatitis, thrombosis and hypersensitivity reactions
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Inova Fairfax Hospital||Falls Church, Virginia 22042-3300|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|Children's Hospital Boston||Boston, Massachusetts 02115|
|Hasbro Children's Hospital||Providence, Rhode Island 02903|
|Columbia University Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian||New York, New York 10032|