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



Status:Active, not recruiting
Conditions:Blood Cancer, Lymphoma
Therapuetic Areas:Oncology
Healthy:No
Age Range:Any - 21
Updated:8/8/2018
Start Date:April 2012
End Date:July 2021

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

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.

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.

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
We found this trial at
7
sites
3300 Gallows Road
Falls Church, Virginia 22042
(703) 776-4001
Inova Fairfax Hospital Inova Fairfax Hospital, Inova's flagship hospital, is an 833-bed, nationally recognized regional...
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Falls Church, VA
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450 Brookline Ave
Boston, Massachusetts 2215
617-632-3000
Dana-Farber Cancer Institute Since it’s founding in 1947, Dana-Farber has been committed to providing adults...
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Boston, MA
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Boston, Massachusetts 02115
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Boston, MA
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Hamilton, Ontario
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Hamilton,
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New York, NY
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New York, New York 10467
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New York, NY
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Providence, Rhode Island 02903
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Providence, RI
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