Trial Information

A Multicenter Phase II Study in Adults With Untreated Acute Lymphoblastic Leukemia: Testing Pharmacokinetically Individualized Doses of L-Asparaginase Following the DFCI Pediatric Consortium Protocol

This study has four treatment phases: 1) induction, 2) central nervous system therapy, 3)
intensification, and 4) continuation.

The induction phase lasts one month and eight drugs are used during this phase of treatment.
The drugs are administered as follows:

- Prednisone; on days 1-28:

- Vincristine; on days 1, 8, 15, and 22:

- Doxorubicin; on days 1 and 2:

- Methotrexate; on day 3;

- Leucovorin; 36 hours after methotrexate:

- Asparaginase; on day 5:

- Intra-thecal Cytarabine; on days 1, 15, and 29:

- Intra-thecal Methotrexate/Hydrocortisone; on days 15 and 29

A bone marrow aspirate and biopsy will be obtained on day 15 and day 29 of induction
therapy. If on day 29, the patients' bone marrow and peripheral blood counts are not in
complete remission, then the patient may receive vincristine on days 29, 36 and 43. Bone
marrow biopsy will be repeated weekly until complete remission is documented. If the
patient does not achieve complete remission by day 49, they will be removed from the study.

Central nervous system (CNS) therapy begins immediately after the end of the induction
therapy. This phase of treatment should last 3 weeks. Treatment includes a series of
spinal taps with the instillation of anti-leukemia drugs. Four spinal taps will be
performed over a two week period. Anti-leukemia drugs will also be given orally. The drugs
given are as follows: Vincristine; on day 1: Doxorubicin; on day 1: 6-mercaptopurine (6-MP);
on days 1-14: Intra-thecal Methotrexate/Cytarabine; 4 times over 2 weeks.

Radiation therapy (RT) will be delivered in 10 daily treatments during the CNS phase of
therapy.

The intensification phase begins as soon as the CNS phase ends and lasts approximately 30
weeks. It consists of cycles of chemotherapy repeated every 3 weeks, along with
asparaginase administered weekly. The drugs given are as follows: Vincristine; day 1:
Dexamethasone; days 1-5: 6-MP; days 1-14: Doxorubicin; day 1: Asparaginase; weekly:
Methotrexate; weekly: Intra-thecal Hydrocortisone/Methotrexate/cytarabine; every 18 weeks.

The continuation phase of treatment begins after the intensification phase. It consists of
cycles of chemotherapy repeated every three weeks and will last until the patient is in
remission for two years. The drugs given are: Vincristine; day 1 : Prednisone or
Dexamethasone; days 1-5: 6-MP; days 1-14: Methotrexate; weekly: Intra-thecal
Methotrexate/Cytarabine/Hydrocortisone: every 18 weeks.

During this study, blood tests will be performed at the start of therapy, at day 29 post
induction and at the time of each intra-thecal therapy (every 18 weeks).

Bone marrow biopsy/aspirate will be done days 15 and 29 of induction, then every 6 months
until completion.