Official Title
Treatment of Acute Lymphoblastic Leukemia in Children
Summary:
The goal of this study is to find new ways to reduce the
side effects of anti-leukemia therapy, and improve the cure rate for this
disease.
The research parts of this study will:
- Compare the differences in toxicity, effectiveness, and
quality of life between two forms ofasparaginase (PEG asparaginase and E. coli
asparaginase)
- Determine whether or not giving more intense treatment to
patients with high minimal residual disease (MRD) levels will improve cure
rates of leukemia
- Learn more about the biology of acute lymphoblastic leukemia
by doing research on blood and bone marrow samples
- Learn how diet may affect the risk of developing side
effects from chemotherapy
Trial Description
- Determine event-free survival rates at 5 years
- Determine asparaginase-related toxicity rates at the
completion of 30 weeks of asparaginase therapy
- Determine rate of infections at the end of a 32-day
remission induction phase
- Determine incidence of neurocognitive toxicities 5-years
from diagnosis
- Monitor quality of life measures during treatment
There are three different treatments being used in this
study, which differ slightly in the types and amounts of chemotherapy drugs.
Patients are assigned to different treatments based on features of their
leukemia, such as their age, white blood cell count, and results of other
tests. The three different groups are called "Standard Risk",
"High Risk" and "Very High Risk".
All treatment groups receive the following phases of
therapy: Prophase, Induction, Consolidation I, central nervous system
(CNS) therapy, Consolidation II and Continuation. Total treatment duration
is 24 months from the date of complete remission.
Research components of the protocol include the Asparaginase
randomization, changing treatment based on minimal residual disease (MRD)
testing, research blood and bone marrow specimens, quality of life questionnaires
and dietary questionnaires.
The Prophase consists of a three-day phase of oral or
intravenous prednisone (day 1, 2 and 3) and intrathecal (in the spinal fluid)
cytarabine (day 1).
The Induction phase starts right after the Prophase. Patients
in the "Standard Risk" group will receive: prednisone orally or
intravenously (days 4-32); vincristine intravenously (days 4, 11, 18, and 25);
doxorubicin intravenously (day 4 and 5); Methotrexate intravenously (day 6) and
intrathecally (day 18 and 32); PEG asparaginase intravenously (day 8);
hydrocortisone intrathecally (day 18); and cytarabine intrathecally (day 18).
Patients in "High Risk" and "Very High Risk" groups will
receive the above medication as well as dexrazoxane intravenously on days 4 and
5.
At the end of the Induction phase blood tests, bone marrow
biopsy and a spinal tap will be performed to determine whether or not the
patient is in remission.
The Consolidation I phase begins directly after the
Induction phase. Patients in the "Standard Risk" group will receive;
vincristine intravenously (day 1); 6-mercaptopurine orally (days 1-14);
methotrexate intrathecally and intravenously (day 1); and leucovorin
intravenously or orally (36 hours after methotrexate). Patients in the
"High Risk" group receive the above medications as well as
doxorubicin intravenously (day 1) and dexrazoxane intravenously (day 1). For
patients in the "Very High Risk" group, the Consolidation phase is
broken down into three sub-phases and involves the same drugs as the "High
Risk" group with the addition of cyclophosphamide, cytarabine, etoposide,
dexamethasone and asparaginase given at different time intervals.
CNS therapy will begin after Consolidation therapy.
Patients in the "Standard Risk" group will receive: Methotrexate/Cytarabine/Hydrocortisone
intrathecally (twice weekly for 4 doses); vincristine intravenously (day 1);
6-mercaptopurine orally (days 1-14); dexamethasone orally (days 1-5); and
asparaginase intravenously or intramuscularly by randomization (IM is 1
dose per week, IV is one dose every other week). Patients in "High
Risk" and "Very High Risk" groups will receive the above drugs
as well as doxorubicin intravenously (day 1) and dexrazoxane intravenously (day
1).
During the CNS stage, some patients in the
"High Risk" and all patients in the "Very High Risk" group
will also receive radiation therapy in 8 or 10 daily treatments (total dose of
1200 or 1800 cGy, depending on whether or not there was leukemia in the spinal
fluid at diagnosis).
Consolidation II stage will begin after the CNS stage and
consists of three-week cycles that last for 30 weeks. Patients in the
"Standard Risk" group will receive: vincristine intravenously (day 1
of each cycle); 6-mercaptopurine orally (day 1-14 of each cycle); dexamethasone
orally (days 1-5 of each cycle); asparaginase either intravenously or
intramuscularly by randomization (IM is once per week, IV is once every other
week); methotrexate intravenously or intramuscularly (one day after
asparaginase); and methotrexate/cytarabine/hydrocortisone intrathecally (every
9 weeks for 6 doses than every 18 weeks). Patients in the "High Risk"
or "Very High Risk" groups will receive the above treatment an in
addition doxorubicin intravenously (day 1 of each cycle) and dexrazoxane intravenously
(day 1 of each cycle). If a patient has received radiation, intrathecal
medications are given less frequently.
The Continuation phase begins after the completion of the
Consolidation II phase. Patients will receive chemotherapy cycles every 3 weeks
until they have been in remission for 2 years. All three groups receive the
same treatment which consists of: vincristine intravenously (day 1 of each
cycle); dexamethasone orally (day 1-5 of each cycle); 6-mercaptopurine orally
(day 1-14 of each cycle); methotrexate intravenously or intramuscularly
(weekly) and methotrexate/cytarabine/hydrocortisone intrathecally (every 18
weeks).
The randomization of asparaginase involves PEG asparaginase
(intravenously) and E. coli asparaginase (intramuscularly). PEG asparaginase
will be given intravenously during the induction phase regardless of the
randomization. Randomized treatment begins in the CNS therapy phase. The
patients decision to take part in the randomization is separate from their
decision to take part in the study as a whole.
Minimal Residual Disease (MRD) testing will be performed at
the end of the induction phase (day 32). It has been found that those children
with higher levels of MRD in their bone marrow have a much higher chance of
relapse than those children who have lower levels. The treatment will change
for subjects with high MRD levels; these patients will be considered very high
risk regardless of their initial risk group classification.
Blood tests, urine tests, spinal taps and bone marrow tests
will be collected throughout the study.
Parents of all subjects will be asked to fill out a Quality
of Life questionnaires about their child's health status. Patients, 12 years of
age or oler, will be asked to complete their own forms.
Parents will also fill out a questionnaire about the types
of food the patient is eating. We hope to learn more about whether different
types of food and vitamins affect the risk of developing side effects from
chemotherapy.
View this trial on ClinicalTrials.gov
