Phase
III Randomized Study of Multidrug Delayed Intensification Therapy in
Children With Newly Diagnosed Standard Risk Acute Lymphocytic Leukemia.
Note:
this outline was patched together from the NCI online protocol and
input from parents of kids with ALL. It is summarized here for our
convenience, so that we can quickly compare our protocols. We do not
guarantee the accuracy of this outline - it is not an official
document. You can contact your child's oncologist and ask for the
complete protocol document if you are interested in the details of your
child's protocol.
cancer.gov
clinical trials search form and
search for 9905, ALL, open trials, phase III
Treatment for standard risk
ALL, defined as presenting features of:
- 1 to 21 at diagnosis
- not qualifying for POG
9904 and
not requiring POG
9906 and not very high risk
(e.g., standard risk - not low, high, or very high risk)
- B precursor ALL
Objectives
- Determine if multidrug
delayed intensification therapy improves outcome in patients with newly
diagnosed standard risk acute lymphocytic leukemia.
- Compare the efficacy and
toxicity of methotrexate administered over 4 hours vs methotrexate
administered over 24 hours in this patient population.
- Determine the correlation
between event free survival, minimal residual disease, and early
response in this patient population treated with this multiple drug
regimen.
Protocol
Outline
All patients receive induction
therapy as per POG
9900. (weeks 1-4)
Induction
(General
Discussion)
3-drug induction (vinc, asp,
dex) (please double check this outline on the COG or the cancer.gov
site)
- ara C IT day 1
- oral dexamethasone twice
daily on days 1-28
- vincristine IV weekly on
days 1, 8, 15, and 22
- (only for high-risk
patients) daunorubicin IV on days 8, 15, 22
- asparaginase IM on days 2,
(PEG?) 5, 8, 12, 15, and 19
- methotrexate (MTX)
intrathecally (IT) on day and 8
- patients with blasts in the
cerebral spinal fluid and inadequate blood counts receive additional
intrathecal therapy on days 15 and 22.
Consolidation
(General
Discussion)
After the 4-week induction:
- patients with M1 bone marrow
and adequate blood counts immediately proceed to consolidation therapy
- patients with M2 bone marrow
receive 2 additional weeks of induction therapy consisting
- oral prednisone three
times a day for 14 additional days
- vincristine IV bolus
- daunorubicin IV over 15
minutes on days 29 and 36
- asparaginase IM on days
29, 32, 36, and 39
- Patients with M1 bone
marrow and adequate blood counts following the above additional
induction therapy immediately proceed to consolidation therapy on day
43.
- Patients with M3 bone marrow
on day 29 or M2 or M3 bone marrow on day 43 are removed from study.
For consolidation, patients are
randomized to one of four treatment arms. Patients with t(1;19) are
randomized to either arm III or arm IV.
Arm I: (weeks 5-24)
- IT MTX on day 1 followed by
MTX IV over 20 minutes followed by MTX continuously over 23.6 hours on
weeks 7, 10, 13, 16, 19, and 22. At 42 hours following the beginning of
the MTX infusion, patients receive oral leucovorin calcium every 6
hours for a total of 3 doses.
- oral mercaptopurine daily
beginning on week 5 and continuing until the completion of
consolidation therapy
- oral dexamethasone twice
daily for 7 days on weeks 8 and 17
- vincristine IV on day 1 of
weeks 8, 9, 17, and 18.
Arm II: (weeks 5-24)
- MTX IV over 4 hours on weeks
7, 10, 13, 16, 19, and 22. At 42 hours following the beginning of the
MTX infusion, patients receive oral leucovorin calcium as in arm I.
- oral mercaptopurine daily
beginning on week 5 and continuing until the completion of
consolidation therapy
- oral dexamethasone twice
daily for 7 days on weeks 8 and 17
- vincristine IV on day 1 of
weeks 8, 9, 17, and 18.
Arm
III: (weeks 5-32) -- Though initially slated for Arm I, Gus did Arm III
of Consolidation at our request (it included a
period of "Delayed Intensification")
- MTX IV as in arm I on weeks
7, 10,13, 24, 27, and 30, leucovorin calcium as in arm I
- asparaginase IM on weeks 16
and 17 for a total of 6 doses
- oral mercaptopurine daily on
weeks 5-13, and from week 24 until the completion of consolidation
therapy
- IT MTX as in arm I on weeks
7, 10, 13, 16, 20, 21, and 30
- oral dexamethasone twice
daily on weeks 8, 16-18, and 28 for a total of 35 days;
- vincristine IV on day 1 of
weeks 8, 9, 16, 17, 18, 28, and 29
- daunorubicin IV on day 1 of
weeks 16-18
- cyclophosphamide IV over 30
minutes on day 1 of week 20
- cytarabine IV or
subcutaneously daily on days 2-5 of weeks 20 and 21
- oral thioguanine daily on
weeks 20-21.
Arm IV: (weeks 5-32)
- MTX IV as in arm II on weeks
7, 10, 13, 24, 27, and 30, leucovorin calcium as in arm I
- asparaginase IM on weeks 16
and 17 for a total of 6 doses
- oral mercaptopurine daily on
weeks 5-13, and from week 24 until the completion of consolidation
therapy
- IT MTX as in arm I on weeks
7, 10, 13, 16, 20, 21, and 30
- oral dexamethasone twice
daily on weeks 8, 16-18, and 28 for a total of 35 days;
- vincristine IV on day 1 of
weeks 8, 9, 16, 17, 18, 28, and 29
- daunorubicin IV on day 1 of
weeks 16-18
- cyclophosphamide IV over 30
minutes on day 1 of week 20
- cytarabine IV or
subcutaneously daily on days 2-5 of weeks 20 and 21
- oral thioguanine daily on
weeks 20-21.
Intensive
continuation therapy (General
Discussion)
At weeks
25-72 for arms I
and
II, and at
weeks
33-80 for arms
III
(in Gus' case this spanned roughly from mid-July of 2005 to mid-July of
2006) and IV, patients
receive
intensive
continuation therapy consisting
of
- MTX every 6 hours for
4
doses on weeks 1, 3, 5, 7, 9, and 11
- oral mercaptopurine
daily
- oral leucovorin
calcium
every 6 hours for 3 doses beginning 42 hours after the start of MTX
- IT MTX on day 1 of
week 12
- vincristine IV on day
1 of
week 12
- oral dexamethasone
twice
daily for 7 days beginning with vincristine
Treatment
repeats every 12
weeks for 4 courses.
Continuation
therapy (General
Discussion)
At weeks 73-130 for arms I and
II, and at weeks 81-130 for arms III and IV, patients receive
continuation therapy consisting of:
- oral MTX weekly
- oral mercaptopurine daily
- vincristine IV on day 1
every 12 weeks
- oral dexamethasone as during
intensive continuation therapy
- IT MTX on day 1 every 12
weeks, beginning with the last week of the first course, in place of
the oral MTX.
Patients are followed
monthly
for 1 year, every 2 months for 1 year, every 3 months for 1 year, every
6 months for 1 year, and then every 6-12 months for 1 year.
Projected
Accrual
A total of 1014 patients will
be accrued for this study over 3.22 years.
General
Disclaimer : These pages are intended for informational purposes only
and are not intended to render medical advice. The information provided
on Ped Onc Resource Center should not be used for diagnosing or
treating a health problem or a disease. It is not a substitute for
professional care. If you suspect your child has a health problem, you
should consult your health care provider.