Augmented Berlin-Frankfurt-Munster (BFM) Therapy for Adolescent/Young Adults With Acute Lymphoblastic Leukemia or Acute Lymphoblastic Lymphoma

Induction:

During Induction, you will receive augmented Berlin-Frankfurt-Munster chemotherapy, which is
made up of a combination of Cerubidine®, Daunorubicin Hydrochloride (daunorubicin), Oncovin®
(vincristine), prednisone, dexamethasone, Oncaspar® (PEG Asparaginase), and MTX amethopterin
(methotrexate). All of these drugs are designed to interfere with the multiplication of
cancer cells to cause them to die and to keep the cancer from coming back.

If you are found to be eligible to take part in this study, on Day 1 or during the spinal tap
procedure, you will be given cytarabine as an injection in your spinal fluid. Within 3 days,
you will begin the Induction course, which will last for 4 weeks.

Daunorubicin and vincristine will be given through a needle in your vein on Days 1, 8,15, and
22. During the first week of therapy, you will be given 1 infusion of PEG Asparaginase by
vein. You will take prednisone by mouth on Days 1-28. Methotrexate will be injected into your
spinal fluid on Weeks 2 and 5 during your spinal tap. Cerebrospinal fluid (CSF) studies will
be sent with each spinal tap to test the fluid for leukemia. If there is disease in your
spinal fluid before starting the treatment, you will be given additional methotrexate doses
once a week until there is no disease present. You will continue to receive methotrexate in
spinal taps every other week for 8 doses, then monthly for 6 doses.

Blood (about 3 teaspoons) will be drawn multiple times during the study for routine tests.
You will have a bone marrow aspirate or biopsy on Days 15 and 29 and then as needed to
confirm remission.

If you have less than 5% immature cells in the bone marrow, 1 week after Induction, you will
continue treatment with Consolidation 1. If you achieved remission after 4 weeks of Induction
treatment, you will then have treatment with Consolidation 1, which will be discussed in a
separate informed consent document.

If you have LL and had no bone marrow involvement at screening, you will have a chest x-ray,
CT scans, and PET scans to measure the disease. Consolidation 1 and other phases of
chemotherapy will be discussed in a separate informed consent document.

If you still have more than 5% leukemia cells in the bone marrow after Induction therapy, you
will receive 2 extra weeks of therapy called "Extended Induction" before going to the next
phase of therapy. You will receive daunorubicin by vein on Day 1. You will receive
vincristine on Weeks 1 and 2 by vein. You will take prednisone by mouth on Days 1-14. You
will receive PEG Asparaginase by vein in the first week of the Extended Induction. Blood
(about 3 teaspoons) will be drawn weekly during the Extended Induction period for routine
tests.

At the end of the Extended Induction period, you will have a physical exam and a bone marrow
aspirate or biopsy to learn your response to treatment.

After Extended Induction, if the disease is in remission, then you will have 1 course of
Consolidation 1, 2 courses of Consolidation 2, and 2 courses of Consolidation 3 before
proceeding to Maintenance therapy. A separate discussion and informed consent document for
Consolidation and Maintenance will be provided.

Length of Study:

You may remain on study for as long as you are benefiting. However, if after Extended
Induction, the disease is not in remission, you will be taken off study, and your doctor will
discuss other treatment options with you.

You may be taken off study if the disease gets worse or comes back during treatment,
intolerable side effects occur, new information becomes available to your study doctor, if
your doctor thinks it is in your best interest, or if you do not attend your appointments,
which are scheduled at least once every 3 months.

This is an investigational study. The chemotherapy drugs used in this study are FDA approved
and commercially available. Up to 125 patients will take part in this study. All will be
enrolled at MD Anderson.

Consolidation and Maintenance:

During Consolidation, you will receive cyclophosphamide, cytarabine, 6-mercaptopurine,
vincristine, PEG asparaginase, methotrexate, doxorubicin, 6-thioguanine, and dexamethasone.
During Maintenance, you will receive, vincristine, dexamethasone, 6-mercaptopurine, and
methotrexate. All of these drugs are designed to interfere with the multiplication of cancer
cells to cause them to die and to keep the cancer from coming back.

If you achieved remission after 4 weeks of induction treatment, you will have treatment with
Consolidation 1, Consolidation 2, Consolidation 3 (Parts A and B), and then you will proceed
to Maintenance therapy.

If the level of blast cells in your blood is above a certain level at Day 15 of Induction but
you achieved complete remission by Day 29, or if you achieved remission after 6 weeks of
induction plus extended induction, then you will receive 1 course of Consolidation 1, 2
courses of Consolidation 2, 2 courses of Consolidation 3 (Parts A and B), and then you will
proceed to maintenance therapy.

Consolidation 1 will last for 8 weeks (2 months). You will receive cyclophosphamide through a
needle in your vein on Weeks 1 and 5. Cytarabine will be given as an injection just beneath
the skin or by vein on or around Days 1-4 and Days 8-11 of each month. 6-Mercaptopurine will
be taken by mouth on Days 1-14 of each month. Vincristine will be given by vein on Weeks 3-4
of each month. PEG Asparaginase will be given by vein on Week 3 and 6 of each month. You will
receive methotrexate through a needle through your spine weekly during Month 1 only. Blood
(about 3 teaspoons) will be drawn for routine tests. You will have a spinal tap with spinal
fluid tests during the intrathecal methotrexate dose. A spinal tap (also called a lumbar
puncture) is when a special needle is inserted into the lower back through the space between
the bones to draw a sample of the fluid that surrounds the spinal cord. You will have a bone
marrow aspiration at the end of Month 2. To collect a bone marrow aspirate, an area of the
hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn
through a large needle.

Consolidation 2 will last for 7 weeks. You will receive vincristine and methotrexate by vein
every 10 plus or minus 2 days for 5 doses. You will receive PEG Asparaginase by vein in Weeks
1 and 4. You will receive intrathecal methotrexate in Weeks 1 and 5. You will have a spinal
tap with spinal fluid tests during the intrathecal methotrexate dose. Blood (about 3
teaspoons) will be drawn every 2 weeks for routine tests.

Consolidation 3 (Part A) will last for 4 weeks. You will receive vincristine and Doxorubicin
by vein in Weeks 1, 2 and 3. Dexamethasone will be taken by mouth on Days 1-7 and Days 15-21.
You will receive PEG Asparaginase by vein on Week 1. You will receive intrathecal
methotrexate in Week 1.

Consolidation 3 (Part B) will last for 4 weeks. You will receive cyclophosphamide by vein in
Week 1. You will receive cytarabine by vein or as an injection for 4 days in a row in Weeks
1-2. You will take 6-Thioguanine by mouth every day for the first 2 weeks. You will receive
intrathecal methotrexate in Weeks 1 and 2. You will receive vincristine by vein on Weeks 3
and 4. You will receive PEG Asparaginase by vein on Week 3.

During Consolidation 3 (Part A and B), blood (about 3 teaspoons) will be drawn at least
weekly for routine tests. Spinal fluid tests will be sent with each intrathecal methotrexate
dose. Spinal taps will be done during each intrathecal chemotherapy dose

Once you finish Consolidation, you will proceed to maintenance therapy.

The Maintenance period for ALL patients will last for 24 months. If you have ALL, you will
receive vincristine by vein every month. You will take dexamethasone by mouth for 5 days
every month. You will take 6-Mercaptopurine by mouth once daily. You will take methotrexate
by mouth every week. You will receive intrathecal methotrexate every 3 months for the first
12 months of maintenance. You will have a spinal tap with spinal fluid tests during the
intrathecal methotrexate dose.

Maintenance for patients with LL will also last for 24 months. If you have LL, you will
receive vincristine by vein every month. You will take dexamethasone by mouth for 5 days
every month.

You will take 6-Mercaptopurine by mouth once daily. You will take methotrexate by mouth every
week.

During the Maintenance period, all participants will have blood samples (about 1 to 3
teaspoons each time) drawn every 3 months for routine tests.

If you have LL, you will have an additional positron emission tomography (PET) scan and
computed tomography (CT) scan at the end of the Maintenance period.

Follow-Up Visits:

Your study doctor will inform you of your follow-up visits in the clinic. At each follow-up
visit there will be a physical exam and complete blood count. You will be followed-up for the
next 3 years after your the last dose of your chemotherapy.

Length of Study:

You may remain on study for as long as you are benefiting. You may be taken off study if the
disease gets worse or comes back during treatment, intolerable side effects occur, new
information becomes available to your study doctor, if your doctor thinks it is in your best
interest, or if you do not attend your appointments, which are scheduled at least once every
3 months.

This is an investigational study. The chemotherapy drugs used in this study are all FDA
approved and commercially available. Up to 125 patients will take part in this study. All
will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients must have precursor-B or T-lymphoblastic leukemia or lymphoblastic lymphoma.

2. Patients must be untreated or have had only one prior chemotherapy regimen for ALL or
LL . Previously treated patients will be analyzed separately.

3. Age between 12 to 40 years old

4. Patients with CNS disease or testicular disease are eligible.

5. Intrathecal therapy with cytarabine is allowed prior to registration for patient
convenience. This is usually done at the time of the diagnostic bone marrow or venous
line placement to avoid a second lumbar puncture. Systemic chemotherapy must begin
within 72 hours of the first intrathecal treatment.

6. Signed informed consent prior to the start of systemic therapy. In the event of
enrollment of a minor patient, an attempt to obtain assent from the patient must be
documented, and parental consent must be signed.

7. Echocardiogram should be done within 72 hours of starting therapy if there are cardiac
risk factors (e.g., history of hypertension or of myocardial infarction)

8. Creatinine should be < 3 mg/dL bilirubin < 3 mg/dl unless felt to be due to disease

9. Zubrod Performance status of <3

10. Patients who received steroids more than 72 hours prior to study enrollment are
eligible but will be analyzed separately

Exclusion Criteria:

1. Age less than twelve years of age or greater than 40 years.

2. More than one prior treatment regimen for ALL or LL.

3. The patient is pregnant or unwilling to practice appropriate birth control.

4. Presence of the Philadelphia chromosome t(9;22)