Trial Information

An Intergroup Phase II Clinical Trial for Adolescents and Young Adults With Untreated Acute Lymphoblastic Leukemia (ALL)

OBJECTIVES:

- To describe the outcomes (i.e., complete response rate, event-free survival,
disease-free survival [DFS], and overall survival [OS]) of adolescents and young adults
with newly diagnosed acute lymphoblastic leukemia (ALL) treated with a pediatric
chemotherapy regimen by adult hematologists/oncologists at multiple sites.

- To explore the feasibility of extending the "pediatric approach" to adult patients up
to 40 years of age.

- To estimate the DFS and OS of these patients.

- To describe the toxicities observed in these patients.

- To compare the outcomes of patients treated on this protocol with appropriate similar
patients (by age and disease characteristics) treated by pediatric oncologists on
protocol COG-AALL0232.

- To evaluate the adherence of adult hematologists/oncologists and their patients to a
"pediatric" ALL treatment regimen and identify reasons for variances.

- To analyze and describe the outcomes of patients treated on this study according to
pretreatment characteristics such as age, gender, white blood cell count, other
hematologic parameters, blood chemistry, immunophenotype, cytogenetics and molecular
genetic characteristics, and treatment variables such as treatment site (academic
center or community), and protocol adherence.

- To analyze and describe the outcomes of patients treated on this study according to
baseline psychosocial characteristics, demographics, and family support.

OUTLINE: This is a multicenter study.

- Remission induction therapy: Patients receive intrathecal (IT) cytarabine on day 1;
vincristine IV on days 1, 8, 15, and 22; prednisone IV or orally twice daily on days
1-28; daunorubicin hydrochloride IV on days 1, 8, 15, and 22; pegaspargase IV or
intramuscularly (IM) on day 4 or 5 or 6; and IT methotrexate on days 8 and 29*.
Patients undergo bone marrow aspirate (BMA) and biopsy on day 29 to assess induction
response and minimal residual disease status. Patients with M1 marrow (< 1%
lymphoblasts) proceed to remission consolidation therapy. Patients with M2 marrow (> 5%
but < 25% lymphoblasts) proceed to extended remission induction therapy. Patients with
M3 marrow are removed from protocol therapy.

NOTE: *Patients with CNS3 disease also receive IT methotrexate on days 15 and 22.

- Extended remission induction therapy: Patients receive prednisone IV or orally twice
daily on days 1-14; vincristine IV on days 1 and 8; pegaspargase IM or IV on day 4 or 5
or 6; and daunorubicin hydrochloride IV on day 1. Patients undergo BMA and biopsy on
day 15. Patients with M1 marrow proceed to remission consolidation therapy. Patients
with M2 or M3 bone marrow are removed from protocol therapy.

- Remission consolidation therapy: Patients receive cyclophosphamide IV on days 1 and 29;
cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; oral
mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50;
pegaspargase IM or IV on days 15 and 43; and IT methotrexate on days 1, 8, 15*, and
22*. Once blood counts recover, patients proceed to interim maintenance therapy.

NOTE: *Patients with CNS3 disease do not receive IT methotrexate on days 15 and 22.

- Interim maintenance therapy: Patients receive vincristine IV and methotrexate (Capizzi
methotrexate) IV on days 1, 11, 21, 31, and 41; pegaspargase IM or IV on days 2 and 22;
and IT methotrexate on days 1 and 31. Once blood counts recover (ANC ≥ 750/mm^3 and
platelet count ≥ 75,000/mm^3), patients proceed to delayed intensification therapy.

- Delayed intensification therapy: Patients receive vincristine IV on days 1, 8, 15, 43,
and 50; dexamethasone IV or orally twice daily on days 1-7 and 15-21; doxorubicin
hydrochloride IV on days 1, 8, and 15; pegaspargase IM or IV on day 4 or 5 or 6 AND day
43; cyclophosphamide IV on day 29; cytarabine IV or SC on days 29-32 and 36-39; oral
thioguanine on days 29-42; and IT methotrexate on days 1, 29, and 36. Once blood counts
recover, patients proceed to maintenance therapy.

- Maintenance therapy: Patients receive vincristine IV on days 1, 29, and 57;
dexamethasone IV or orally twice daily on days 1-5, 29-33, and 57-61; mercaptopurine
orally on days 1-84; IT methotrexate on day 1*; and oral methotrexate on days 8, 15,
22, 29**, 36, 43, 50, 57, 64, 71, and 78.

Treatment repeats every 12 weeks for 2 years from the start of interim maintenance (for
female patients) or 3 years from the start of interim maintenance (for male patients).

NOTE: *IT methotrexate is also given on day 29 of the first 4 courses of maintenance
therapy.

NOTE: **Oral methotrexate is held on day 29 of the first 4 courses of maintenance therapy
(when IT methotrexate is given).

- Radiotherapy: During the first course of maintenance therapy, patients with testicular
disease undergo concurrent radiotherapy to the testes 5 days a week for 2.5 weeks
(total dose 2400 cGy given in 12 daily fractions); patients with CNS3 disease undergo
concurrent cranial radiotherapy 5 days a week for 2 weeks (total dose of 1800 cGy given
in 10 daily fractions); and patients with T-cell ALL undergo concurrent cranial
radiotherapy (total dose of 2400 cGy given in 10 daily fractions) 5 days a week for 2
weeks.

Patients may complete surveys at the end of courses 1, 2, and 4, at the end of all protocol
treatment, and at 6 and 18 months after the end of all protocol treatment.

After completion of study treatment, patients are followed every 1-3 months for 3 years and
then every 6 months for 7 years.