Trial Information

Phase II Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage

The augmented hyper-CVAD chemotherapy is a combination of chemotherapy drugs including
cyclophosphamide, vincristine, adriamycin, dexamethasone, and pegaspargase given together
for one "course" of treatment. It is called "augmented" because additional drugs are being
added to the hyper-CVAD combination, which is the standard combination of chemotherapy drugs
for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma. This switches
back and forth with a course of the chemotherapy drugs methotrexate and ara-C (also with
vincristine, dexamethasone, and pegaspargase).

Before treatment starts, you will have a physical exam, including blood (about 8 teaspoons)
tests. You will also have a bone marrow sample taken; the sample will be taken through a
large needle in the hipbone.

All participants will receive 2 kinds of chemotherapy courses for a total of 8 courses.
Chemotherapy courses will be given through a large vein by a central venous catheter (a
plastic tube usually placed under the collarbone).

During treatment, you will have a physical exam and give blood samples (about 1 tablespoon
each) at least twice a week. A bone marrow sample will be repeated 2-3 weeks after the
start of treatment to check the response, and later as needed.

Course 1 will include cyclophosphamide given by vein over 2-3 hours every 12 hours. This
will be given for 6 doses over 3 days (Days 1, 2 and 3). Adriamycin will be given by vein
over 24 hours on Day 4. Vincristine will be given by vein over 15 to 30 minutes on Days 1,
8, and 15. Dexamethasone (a steroid) will be given by mouth or by vein on Days 1 to 4 and
15-18. Pegaspargase will be given by vein over 1-2 hours on Day 1.

G-CSF (growth colony stimulating factor) will be given starting 24 hours after each course
of chemotherapy is finished (Day 5 or 6). It is given to help with rapid recovery of the
normal bone marrow. G-CSF will be injected by vein or under the skin until the blood counts
recover.

Treatment to the brain will be given inside the spinal fluid (spinal tap) with ara-C and
methotrexate on Days 2 and 7 of Courses 1 and 2 for a total of 4 treatments. This is done
to decrease the risk that the leukemia will develop there.

During Course 2, you will receive methotrexate by infusion over 24 hours on the first day
and ara-C by vein at a high dose over 2 hours every 12 hours for 4 doses (Days 2 and 3).
You will also receive vincristine (Days 1, 8, and 15), dexamethasone (Days 1-4 and 15-18),
and pegaspargase (Day 5).

Citrovorum factor (leucovorin), an antidote for side effects of methotrexate, will be given
by vein or by mouth for 2-3 days (Day 2 and on). G-CSF will be given as in Course 1 (24
hours after the chemotherapy is finished). The treatment to the brain inside the spinal
fluid will be given as in Course 1 on Days 2 and 7.

The schedule of chemotherapy will switch between hyper-CVAD (Courses 3, 5, and 7) and
methotrexate/ara-C (Courses 4, 6 and 8) to complete a total of 8 courses. After the 8
courses, you will go on maintenance chemotherapy. This includes daily 6-mercaptopurine
taken by mouth, weekly methotrexate by vein or mouth, monthly vincristine by vein, and
prednisone by mouth for 5 days every month. Maintenance therapy will continue for one year.

Treatment will be given on an inpatient or outpatient basis for the 8 intensive courses of
chemotherapy, as indicated by your condition. The maintenance treatments may be given as an
outpatient. Patients will be taken off study if the disease gets worse or if intolerable
side effects occur.

This is an investigational study. All of the drugs are commercially available. Their use
together in this study is investigational. About 90 patients will take part in this study.
All will be enrolled at UT MD Anderson Cancer Center.