Official Title
A Phase 3 Trial Investigating Blinatumomab (NSC# 765986) in Combination With Chemotherapy in Patients With Newly Diagnosed Standard Risk or Down Syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients With Localized B-Lymphoblastic Lymphoma (B-LLy)
Summary:
This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better than combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.
Trial Description
Primary Outcome:
- Disease free survival (DFS) in randomization eligible patients with higher risk features (SR-High) or standard risk average (SR-Avg) B-ALL patients based on randomization with addition of blinatumomab
- DFS in boys in the SR-favorable subset of SR B-ALL with or without Down syndrome (DS)
Secondary Outcome:
- DFS for patients with SR-Avg B-ALL who are negative for MRD measured by flow cytometry and HTS at EOI when treated with standard chemotherapy with a treatment duration of 2 years from the start of interim maintenance (IM)1, regardless of sex
- DFS for patients with standard-risk favourable (SR-Fav) B-ALL when treated with a standard chemotherapy regimen
- Treatment-related mortality in Down syndrome high risk (DS-high) patients after replacement of intensive elements of standard chemotherapy (omission of anthracyclines in induction, omission of the second month of DI) with 3 cycles of blinatumomab
- DFS of DS-High B-ALL patients when intensive elements of chemotherapy are replaced with 3 cycles of blinatumomab
- DFS of patients with localized B-lymphoblastic lymphoma (B-LLy) receiving standard risk acute lymphoblastic leukemia therapy
- Change in neurocognitive functioning from baseline to end-of-therapy between children from poor (defined as presence of household material hardship [HMH], including either food, housing or energy insecurity) and non-poor families (absence of HMH)
- Caregiver burden as measured by the Mean Total score from the Care of My Child with Cancer questionnaire among a subset of children enrolled in the HMH and neurocognitive outcome study
- Caregiver burden as measured by the At-Work Productivity Loss summary score from the Caregiver Work Limitations questionnaire among a subset of children enrolled in the HMH and neurocognitive outcome study
PRIMARY OBJECTIVES:
- To determine in a randomized manner if the addition of 2
cycles of blinatumomab to standard therapy improves disease-free survival (DFS)
in patients with standard risk (SR) B-ALL and higher risk features (SR-High),
and patients with standard-risk average (SR-Avg) B-ALL who are negative for
minimal residual disease (MRD) by flow cytometry but have detectable or indeterminate
MRD as measured by high-throughput sequencing (HTS) at end of induction (EOI).
- To confirm that boys in the standard-risk favorable (SR-Fav)
subset of B-ALL, with or without Down syndrome (DS), will maintain a 5-year DFS
of greater than 93% when treated with a standard chemotherapy regimen with a
treatment duration of 2 years from the start of interim maintenance I (IM1).
SECONDARY OBJECTIVES:
- To describe the DFS for patients with SR-Avg B-ALL who are
negative for MRD measured by flow cytometry and HTS at EOI when treated with
standard chemotherapy with a treatment duration of 2 years from the start of
IM1, regardless of sex.
- To describe the DFS for patients with standard-risk
favorable (SR-Fav) B-ALL when treated with a standard chemotherapy regimen.
- To determine if patients with DS-High achieve a reduction of
treatment-related mortality (TRM) after replacement of intensive elements of
standard chemotherapy (omission of anthracyclines in induction, omission of the
second month of delayed intensification [DI]) with 3 cycles of blinatumomab.
- To describe the DFS characterized by the replacement of
intensive elements of standard chemotherapy with 3 cycles of blinatumomab in
patients with DS-High B ALL.
- To describe the DFS for patients with localized (Murphy
stage I and II) B lymphoblastic lymphoma (B-LLy) receiving standard risk B-ALL
therapy.
- To compare the change in neurocognitive functioning, as
measured by the CogState Cognitive Composite, from baseline to end-of-therapy
among patients with ALL ages 4- < 10 years at the time of diagnosis between
children from poor families (defined as presence of household material hardship
[HMH], including either food, housing or energy insecurity) and non-poor
families (absence of HMH).
- To describe the impact of blinatumomab on caregiver burden
and patient/proxy-reported symptoms among a subset of children enrolled in the
HMH and neurocognitive outcome study.
EXPLORATORY OBJECTIVES:
- To explore adaptive and innate immune functions and host
genetic factors associated with severe infectious complications in children
with DS B-ALL.
- To explore the impact of acute lymphoblastic leukemia (ALL)
and its therapy on neurocognitive, functional, and quality of life outcomes in
patients with DS and ALL, as measured by caregiver (parent/legal guardian)
questionnaires.
- To define the prevalence of minimal marrow disease (MMD) in
B-LLy and to correlate MMD at diagnosis with outcome in patients with B-LLy.
OUTLINE: All patients are assigned to, and complete an
INDUCTION treatment regimen. Patients are then assigned to a CONSOLIDATION
treatment regimen. Finally, following CONSOLIDATION, patients are either
assigned or randomized to 1 of 7 arms.
NON-DS SR B-ALL INDUCTION: Patients receive cytarabine
intrathecally (IT) on day 1, vincristine intravenous (IV) push over 1 minute on
days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on
days 1-28, pegaspargase IV over 1-2 hours or intramuscularly (IM) on day 4, and
methotrexate IT on days 8 and 29. CNS2 patients also receive cytarabine IT
twice weekly except during weeks when days 8 and 29 methotrexate is
administered. Treatment continues for 35 days in the absence of disease progression
or unacceptable toxicity.
* After Non-DS SR B-ALL INDUCTION, SR-Fav and SR-Avg
patients complete SR CONSOLIDATION, while patients with SR-High complete
high-risk (HR) CONSOLIDATION.
DS B-ALL INDUCTION: Patients receive cytarabine IT on day 1,
vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV
over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin
PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients
under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and
patients 10 years of age or older receive prednisone or prednisolone PO or IV
BID on days 1-28. CNS2 patients also receive cytarabine IT twice weekly except
during weeks when days 8 and 29 IT methotrexate is administered. CNS3 patients
also receive methotrexate IT on days 15 and 22, and leucovorin PO or IV every 6
hours for 2 doses on days 16 and 23. Treatment continues for 35 days in the
absence of disease progression or unacceptable toxicity.
* After DS B-ALL INDUCTION, patients without high risk
features and MRD < 0.01 % complete SR CONSOLIDATION. Patients without high
risk features and MRD >= 0.01%, OR with high risk features and any MRD
complete HR CONSOLIDATION.
NON-DS B-LLy INDUCTION: Patients receive cytarabine IT on
day 1 and twice weekly if CNS2, vincristine IV push over 1 minute on days 1, 8,
15, and 22, dexamethasone PO or IV BID on days 1-28, pegaspargase IV over 1-2
hours or IM on day 4, and methotrexate IT on days 8 and 29. Treatment continues
for 35 days in the absence of disease progression or unacceptable toxicity.
* After NON-DS B-LLy INDUCTION, all B-LLy patients then
complete SR CONSOLIDATION.
DS B-LLY INDUCTION: Patients receive cytarabine IT on day 1,
vincristine IV push over 1 minute on days 1, 8, 15, and 22, pegaspargase IV
over 1-2 hours or IM on day 4, methotrexate IT on days 8 and 29, and leucovorin
PO or IV every 6 hours for 2 doses on days 9 and 30. Additionally, patients
under 10 years of age receive dexamethasone PO or IV BID on days 1-28, and
patients 10 years of age or older receive PO or IV prednisone or
methylprednisolone on days 1-28. Treatment continues for 35 days in the absence
of disease progression or unacceptable toxicity.
* After DS B-LLy INDUCTION, patients then complete SR
CONSOLIDATION.
SR CONSOLIDATION: Patients receive vincristine IV push over
1 minute on day 1, mercaptopurine PO on days 1-28, and methotrexate IT on days
1, 8, and 15. DS patients also receive leucovorin PO or IV every 6 hours for 2
doses on days 2, 9, and 16. Treatment continues for 28 days in the absence of
disease progression or unacceptable toxicity.
* After SR CONSOLIDATION, patients with MRD undetectable are
assigned to ARM A, and patients with MRD detectable/indeterminate/unavailable
are randomized to ARM A or B. Patients with SR-Fav and all B-LLy patients are
assigned to treatments identical to that in ARM A.
HR CONSOLIDATION: Patients receive cyclophosphamide IV over
30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days
1-4, 8-11, 29-32, and 36-39, vincristine IV push over 1 minute on days 15, 22,
43, and 50, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days
1, 8, 15, and 22 , and pegaspargase IV over 1-2 hours or IM on days 15 and 43.
DS patients also receive leucovorin PO or IV every 6 hours for 2 doses on days
2, 9, 16, and 23 (on days 2 and 9 only for DS CNS3 patients). Treatment
continues for 56 days in the absence of disease progression or unacceptable
toxicity. Patients with continued clinical evidence of DS or testicular
leukemia (from diagnosis through the end of Induction) undergo testicular
radiation therapy over 12 fractions once daily (QD).
* After HR CONSOLIDATION, patients are randomized to ARM C
or D. DS B-ALL patients with MRD < 1% are assigned to an arm including three
blocks of blinatumomab.
ARM A:
INTERIM MAINTENANCE I: Patients receive vincristine IV push
over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes
(undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and
methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6
hours for 2 doses on day 32. Treatment continues for 56 days in the absence of
disease progression or unacceptable toxicity.
DELAYED INTENSIFICATION: Patients receive methotrexate IT on
day 1 and 29, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV
push over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15
minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4,
cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42,
and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and
36-39. DS patients receive leucovorin PO or IV every 6 hours for 2 doses on
days 2 and 30. Treatment continues for 56 days in the absence of disease
progression or unacceptable toxicity.
INTERIM MAINTENANCE II: Patients receive vincristine IV push
over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes
undiluted or 10-15 minutes diluted on days 1, 11, 21, 31, and 41, and
methotrexate IT on days 1 and 31. DS patients receive leucovorin PO or IV every
6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in the
absence of disease progression or unacceptable toxicity.
MAINTENANCE: Non-DS patients receive methotrexate IT on day
1, vincristine IV push over 1 minute on day 1, dexamethasone PO on days 1-5,
mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36,
43, 50, 57, 64, 71, and 78. DS patients receive vincristine IV push over 1
minute on day 1, methotrexate IT on day 1, dexamethasone PO on days 1-5,
mercaptopurine PO on days 1-84, and methotrexate PO on days 8, 15, 22, 29, 36,
43, 50, 57, 64, 71, and 78, and leucovorin IV or PO on day 2 if DS. Treatment
repeats every 84 days until a total duration of therapy of 2 years from start
of INTERIM MAINTENANCE I is reached in the absence of disease progression or
unacceptable toxicity.
ARM B:
BLINATUMOMAB BLOCK I: Patients receive dexamethasone IV or PO
on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days
1-28. DS patients also receive leucovorin IV or PO every 6 hours for 2 doses on
day 2. Treatment continues for 35 days in the absence of disease progression or
unacceptable toxicity.
INTERIM MAINTENANCE I: Patients receive vincristine IV push
over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes
(undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and
methotrexate IT on day 31. DS patients also receive leucovorin PO or IV every 6
hours for 2 doses on day 32. Treatment continues for 56 days in the absence of
disease progression or unacceptable toxicity.
BLINATUMOMAB BLOCK II: Patients receive methotrexate IT on
day 1, and blinatumomab IV continuously on days 1-28. DS patients also receive
leucovorin PO or IV every 6 hours for 2 doses on day 2. Treatment continues for
35 days in the absence of disease progression or unacceptable toxicity.
DELAYED INTENSIFICATION: Patients receive methotrexate IT on
day 1 and 29, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV push
over 1 minute on days 1, 8, and 15, doxorubicin IV push/infusion over 1-15
minutes on days 1, 8, and 15, pegaspargase IV over 1-2 hours or IM on day 4,
cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42,
and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients
receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and 30.
Treatment continues for 56 days in the absence of disease progression or
unacceptable toxicity.
INTERIM MAINTENANCE II: Patients receive vincristine IV push
over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes
(undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and
methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV
every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in
the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Non-DS patients receive methotrexate IT on day
1 (omit on final 2 cycles), vincristine IV push over 1 minute on day 1,
dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and methotrexate
PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 1 on final
2 cycles). DS patients receive methotrexate IT on day 1 (omit on final 2
cycles), dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84, and
methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit
day 1 except for final 2 cycles), for DS patients and leucovorin IV or PO every
6 hours for 2 doses on day 2 (omit on final 2 cycles). Treatment repeats every
84 days until a total duration of therapy of 2 years from start of INTERIM
MAINTENANCE I is reached in the absence of disease progression or unacceptable
toxicity.
ARM C:
INTERIM MAINTENANCE I: Patients receive vincristine IV push
over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1,
15, 29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56,
methotrexate IT on day 1 and 29, and leucovorin PO or IV on days 3-4, 17-18,
31-32, and 45-46. Treatment continues for 56 days in the absence of disease
progression or unacceptable toxicity.
DELAYED INTENSIFICATION: Patients receive methotrexate IT on
day 1, dexamethasone PO BID or IV on days 1-7 and 15-21, vincristine IV over 1
minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days
1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43,
cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42,
and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment
continues for 56 days in the absence of disease progression or unacceptable
toxicity.
INTERIM MAINTENANCE II: Patients receive vincristine IV over
1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5
minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and
41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on
days 2 and 22. Treatment continues for 56 days in the absence of disease
progression or unacceptable toxicity.
MAINTENANCE: Patients receive vincristine IV over 1 minute
on day 1, prednisone or prednisolone or methylprednisolone PO or IV on days
1-5, mercaptopurine PO on days 1-84, methotrexate IT on days 1 and 29 of cycles
1-2 and on day 1 of subsequent cycles, methotrexate PO on days 8, 15, 22, 29
(for cycle 3 and later only), 36, 43, 50, 57, 64, 71, and 78. Treatment repeats
every 84 days until a total duration of therapy of 2 years from start of
interim maintenance I is reached in the absence of disease progression or
unacceptable toxicity.
ARM D:
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or
IV on day 1, methotrexate IT on day 1, and blinatumomab IV continuously on days
1-28. Treatment continues for 35 days in the absence of disease progression or
unacceptable toxicity.
INTERIM MAINTENANCE I: Patients receive vincristine IV over
1 minute on days 1, 15, 29, and 43, high dose methotrexate IV on days 1, 15,
29, and 43, mercaptopurine PO on days 1-14, 15-28, 29-42, and 43-56,
methotrexate IT on days 1 and 29, and leucovorin PO or IV on days 3-4, 17-18,
31-32, and 45-46. Treatment continues for 56 days in the absence of disease
progression or unacceptable toxicity.
BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on
days 1-28 and methotrexate IT on day 1. Treatment continues for 35 days in the
absence of disease progression or unacceptable toxicity.
DELAYED INTENSIFICATION: Patients receive methotrexate IT on
day 1, dexamethasone PO or IV on days 1-7 and 15-21, vincristine IV over 1
minute on days 1, 8, 15, 43, and 50, doxorubicin IV over 1-15 minutes on days
1, 8, and 15, pegaspargase IV over 1-2 hours or IM on days 4 and 43,
cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42,
and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. Treatment
continues for 56 days in the absence of disease progression or unacceptable
toxicity.
INTERIM MAINTENANCE II: Patients receive vincristine IV over
1 minute on days 1, 11, 21, 31, and 41, Capizzi style methotrexate IV over 2-5
minutes (undiluted) or over 10-15 minutes (diluted) on days 1, 11, 21, 31, and
41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM
on days 2 and 22. Treatment continues for 56 days in the absence of disease
progression or unacceptable toxicity.
MAINTENANCE: Patients receive methotrexate IT on day 1,
vincristine IV over 1 minute on day 1, prednisone, prednisolone or methylprednisolone
PO or IV on days 1-5, mercaptopurine PO on days 1-84, and methotrexate PO on
days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 84
days until a total duration of therapy of 2 years from start of interim
maintenance I is reached in the absence of disease progression or unacceptable
toxicity.
DS-HIGH B-ALL:
BLINATUMOMAB BLOCK I: Patients receive dexamethasone PO or
IV on day 1, blinatumomab IV continuously on days 1-28, methotrexate IT on day
1 (or on day 56 of Consolidation), and leucovorin PO or IV every 6 hours for 2
doses on day 2. Treatment continues for 35 days in the absence of disease
progression or unacceptable toxicity.
INTERIM MAINTENANCE: Patients receive vincristine IV push
over 1 minute on days 1, 15, 29, and 43, intermediate dose methotrexate IV over
24 hours on days 1, 15, 29, and 43, mercaptopurine PO on days 1-14, 15-28,
29-42, and 43-46, methotrexate IT on days 1 and 29, and leucovorin PO or IV
every 6 hours for 2 doses on days 2-4, 16-18, 30-32, and 44-46. Treatment
continues for 63 days in the absence of disease progression or unacceptable
toxicity.
BLINATUMOMAB BLOCK II: Patients receive blinatumomab IV on
days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for
2 doses on day 2. Treatment continues for 35 days in the absence of disease
progression or unacceptable toxicity.
DELAYED INTENSIFICATION: Patients receive vincristine IV
over 1 minute on days 1, 8, and 15, doxorubicin IV over 1-15 minutes on days 1,
8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate IT on day
1, leucovorin PO or IV every 6 hours for 2 doses on day 2, and pegaspargase IV
over 1-2 hours or IM on day 4. Treatment continues for 28 days in the absence
of disease progression or unacceptable toxicity.
BLINATUMOMAB BLOCK III: Patients receive blinatumomab IV on
days 1-28, methotrexate IT on day 1, and leucovorin PO or IV every 6 hours for
2 doses on day 2. Treatment continues for 35 days in the absence of disease
progression or unacceptable toxicity.
MAINTENANCE: Patients receive vincristine IV push over 1
minute on day 1, prednisone, prednisolone or methylprednisolone PO or IV BID on
days 1-5, mercaptopurine PO on days 1-84, methotrexate IT on day 1,
methotrexate PO on days 8, 15, 22, 29 (omit day 29 for first 3 cycles for
patients who do not receive cranial radiotherapy), 36, 43, 50, 57, 64, 71, and
78, and leucovorin PO on days 2 and 30 (day 30 dose is for cycles 1-3 and for
patients who do not receive cranial radiotherapy). CNS3 patients receive
cranial radiotherapy during first 4 weeks of cycle 1. Treatment repeats every
84 days until a total duration of therapy of 2 years from start of interim
maintenance I is reached in the absence of disease progression or unacceptable
toxicity.
All B-LLy patients:
INTERIM MAINTENANCE I: Patients receive vincristine IV push
over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes
(undiluted) or 10-15 (diluted) on days 1, 11, 21, 31, and 41, and methotrexate
IT on day 31. DS patients also receive leucovorin PO or IV every 6 hours for 2
doses on day 32. Treatment continues for 56 days in the absence of disease
progression or unacceptable toxicity.
DELAYED INTENSIFICATION: Patients receive vincristine IV
push over 1 minute on days 1, 8 and 15, doxorubicin IV over 1-15 minutes on
days 1, 8, and 15, dexamethasone PO or IV on days 1-7 and 15-21, methotrexate
IT on days 1 and 29, pegaspargase IV over 1-2 hours or IM on day 4,
cyclophosphamide IV over 30-60 minutes on day 29, thioguanine PO on days 29-42,
and cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39. DS patients
additionally receive leucovorin PO or IV every 6 hours for 2 doses on days 2 and
30. Treatment continues for 56 days in the absence of disease progression or
unacceptable toxicity.
INTERIM MAINTENANCE II: Patients receive vincristine IV push
over 1 minute on days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes
(undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41, and
methotrexate IT on days 1 and 31. DS patients also receive leucovorin PO or IV
every 6 hours for 2 doses on days 2 and 32. Treatment continues for 56 days in
the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive vincristine IV push over 1
minute on day 1, dexamethasone PO on days 1-5, mercaptopurine PO on days 1-84,
methotrexate IT on day 1, and methotrexate PO on days 8, 15, 22, 29, 36, 43,
50, 57, 64, 71, and 78. DS patients also receive leucovorin PO or IV every 6
hours for 2 doses on day 2. Treatment repeats every 84 days until a total
duration of therapy of 2 years from start of interim maintenance I is reached
in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed
up every 4 weeks until complete blood count(CBC)/differential/platelet count
recovery, then every 3 months for the first 2 years, then every 4-6 months for
the 3rd year, and every 6-12 months for the 4th and 5th years.
View this trial on ClinicalTrials.gov
