IRB Number:

07-001427

Trial Status:

Open for Enrollment

Phase: III

Why is this study being done?

Acute lymphoblastic leukemia (ALL) is a type of cancer that occurs in the bone marrow. It is a disease in which there is an uncontrolled growth of abnormal white blood cells, referred to as blasts. These abnormal cells crowd out the normal cells in the bone marrow. Sometimes these blasts cells can be found in the brain, spinal cord, and/or other organs of the body. It is common to enroll children and adolescents with cancer in a clinical trial that seeks to improve cancer treatment over time. Clinical trials include only people who choose to take part. You have a choice between a standard treatment for T-cell ALL and this clinical trial.

What Is The Current Standard Of Treatment For This Disease?
In the first stage, called Induction, the medical team tries to remove all visible signs of leukemia and allow normal blood cells to be restored (this is called remission). Six chemotherapy drugs are used during this stage of treatment. The leukemia treatment is the same for patients who choose to be on this study and those who do not.

The following is detailed information on the current standard of Induction therapy:

Standard Treatments and Procedures for Patients with T cell ALL

Central Line
For drugs to be given by vein, the doctor will likely recommend that the patient have a central venous line placed.

Methods for Giving Drugs
Various methods will be used to give drugs to patients.
- PO - Drug is given by tablet or liquid swallowed through the mouth.
- IV - Drug is given using a needle or tubing inserted into a vein. It can be given by IV push over several minutes or by infusion over minutes or hours.
- IM - Drug is given using a needle injected into the muscle.
- SQ - Drug is given by injecting a needle into the tissue just under the skin.
- IT - Drug used to treat the brain and spinal cord is given using a needle inserted into the fluid surrounding the spinal cord.

Most drugs used on this study will be given using a needle or tubing inserted into the vein (IV).

Therapy for patients on all treatment plans:
The purpose of Induction therapy is to kill as many of the leukemia cells as possible so the disease goes into remission.

Drugs/ How the drug will be given/ Days
Cytarabine IV or SQ Day 1
Vincristine IV Days 1, 8, 15, 22
Prednisone PO or IV Days 1 - 28
Daunorubicin IV Days 1, 8, 15, 22
PEG Asparaginase* IM Days 4 [or 5 or 6]
Methotrexate** IT Days 8, 29
Leucovorin (patients with Down syndrome ONLY) PO 48 and 60 hours following each IT MTX

*If patients develop an allergy to PEG asparaginase, six injections of a different form of asparaginase (called Crisantaspase) may be substituted for each dose of PEG asparaginase

**If patients have leukemia in the spinal fluid of the first spinal tap they may also get methotrexate on Days 15 and 22


Standard tests and procedures
The following tests and procedures are part of regular cancer care and may be done even if the patient does not join the study.
- Physical exams
- Frequent labs to monitor blood counts and blood chemistries
- Urine tests to measure how the kidneys are functioning
- Pregnancy test for females of childbearing age before treatment begins
- X-rays and scans to monitor the patient's response to treatment
- Tests to monitor heart and lung functioning
- Bone marrow aspirations to see if the leukemia is responding to treatment
- Spinal taps to check for leukemia cells in the spinal fluid and to give chemotherapy into the spinal fluid

Measurement of Early Response to Treatment
During Induction therapy, tests will be done on the patient's bone marrow samples to let the researchers know how well the patient is responding to treatment. Two types of tests will be done.
1. The patient's local hospital laboratory will perform standard tests to measure how much leukemia is still left.
2. The central Children's Oncology Group (COG) laboratory will use a specialized test to measure minimal residual disease. This test detects numbers of leukemia cells that are too small to be seen by human eyes.

Using the results of these tests, in combination with the patient's age and white blood cell count at diagnosis and whether or not the patient had leukemia in their spinal fluid or testicles, researchers will then be able to place the patient into one of four categories:

1. Low Risk: These patients are less than 10 years old and have a white blood cell count of less than 50,000 at diagnosis, without evidence of testicular disease or leukemia in the central nervous system. In addition, these patients have very few or no leukemia cells in the bone marrow tested in your local hospital by Day 8 or Day 15 and there is little minimal residual disease found in the bone marrow tested at the COG laboratory from Day 29. Low Risk patients will not take part in the study of the new drug, nelarabine, nor will they receive radiation therapy since they are expected to do well with standard treatment.
2. Intermediate Risk: This group included all of those patients who do not meet criteria or fit the definition for Low Risk, High Risk or patients who still have T cell leukemia at the end of Induction.
3. High Risk: Regardless of any other features or test results, these patients have 5 percent to 25 percent blasts visible under the microscope on Day 29 of Induction therapy OR more than 1 percent blasts detected by a special test for minimal residual disease (MRD).
4. Patients with T cell leukemia at the end of Induction: Regardless of any other features or tests results, these patients have more than 25 percent blasts visible under the microscope on Day 29 of Induction therapy.

The term "risk" refers to the chance of the cancer coming back after treatment. Once the researchers have measured the patient's early response to treatment, they will be able to find out which of these risk categories of T cell ALL the patient belongs to. This will help determine the amount of chemotherapy the patient will need for the second part of the treatment.

Who is Eligible to Participate in the Study?

-Age one year old to age 30 years
-Newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL)

*More specific, detailed eligibility and/ or exclusion criteria are associated with this trial.

What is Involved With this Study?

Why Is This Study Being Done?
The overall goal of this study is to see if the researchers can increase the cure rate for T cell ALL with acceptable side effects of therapy. Side effects are unintended and unwanted results of treatment.

The purpose of Part I of this study is to collect information on leukemia and the effects of Induction therapy. If the patient takes part in Part I of this study, they have the option to take part in Part II, which is an experimental option for the next part of the patient's treatment.

During and at the end of Induction, tests will be done on the bone marrow samples to find out how well the treatment is working. This helps the study doctors know how strong the rest of the patient's treatment needs to be to keep the leukemia in remission. Patients will be offered the chance to take part in Part II of this study once their T cell ALL risk category and response to this Induction therapy is known.

Phase 2
Patients with High Risk leukemia will receive one of four treatment arms. The four different treatment arms will allow the research staff to evaluate two experimental treatments:
1. High-dose intravenous (IV) methotrexate along with leucovorin, a medicine to decrease the side effects of methotrexate, and oral 6-mercaptopurine vs. the standard lower escalating doses of IV methotrexate with intramuscular peg-asparaginase
2. Nelarabine, a drug that may be effective in patients with T cell leukemia, when given to patients with T-ALL who were also receiving therapy very similar to that recommended here.

Patients with Intermediate Risk leukemia will receive one of two treatment plans in Phase 1, either the standard treatment plan or the experimental treatment plan. The experimental treatment plan is the same as the standard treatment plan but with two differences: (1) the drug methotrexate is given differently and (2) the patient will receive a drug called 6-marcaptopurine instead of pegaspargase. This research study will test whether the experimental treatment plan is more effective than the current standard of care. The researchers want to know if it cures more children with T cell ALL than standard treatment.

The purpose of this part of the study is to compare the effects, good and/or bad, of two different treatment plans for Low Risk T cell ALL.
One treatment plan is a standard chemotherapy regimen for Low Risk T cell ALL. The experimental treatment plan is the same as the standard treatment plan, but with two differences: (1) the drug methotrexate is given differently and (2) patients will receive a drug called 6-mercaptopurine instead of pegaspargase. In the experimental treatment plan methotrexate is given on fewer occasions but at a higher dose. Because the dose of methotrexate is higher, the experimental treatment arm will require four additional hospital stays at 3-4 days each. This research study will test whether the experimental treatment plan is more effective than the current standard of care. The researchers want to know if it cures more children with Low Risk T cell ALL than standard treatment.

Induction Failure
If patients take part in this study, they will receive Augmented Therapy with the addition of the experimental drug nelarabine. In addition, one phase of the standard augmented therapy will be modified. Their therapy will include four courses of high-dose methotrexate instead of the standard five courses of lower dose escalation IV methotrexate given as past of the standard augmented therapy. Each of the four courses of high-dose methotrexate will require a 3 to 4 day hospital stay. It is hoped that high-dose methotrexate and nelarabine will allow the patient to achieve and stay in remission.

How long will the Study run?

Induction will last five weeks. Patients will be given the chance to continue on Part II of this clinical trial once their doctor knows the patient's T-cell ALL sub-type and how much leukemia is left in their bone marrow. Patients will need to get more therapy for leukemia whether or not they take part in Part II. After treatment, patients will have follow-up examinations and medical tests. The research staff will continue to collect some medical information about how they are doing for 10 years after the last patient starts the study.

Sponsor(s): Children's Oncology Group (COG)

Study Activation/Registration Date: 11/27/2007

IRB Review and Approval Date: 09/25/2007

Study Type: Treatment

Projected Accrual: The plan is to have up to 1380 patients participate from multiple medical centers.

Costs of Study:There may be standard patient care costs related to participating in a cancer research study.

Principal Investigator: Vilmarie Rodriguez, MD

Who can I Contact for Additional Information on this Trial?

Complete Request Form for Cancer Clinical Trial Information at Mayo Clinic or
For more information about this study or other clinical trial options, please contact our Mayo Clinic Cancer Center Clinical Trials Referral Office.

• Patients living within the United States, call 507-538-7623, or e-mail cancerclinicaltrials@mayo.edu


• Patients living outside the United States may call our International Office at 507-284-8884, or e-mail intl.mcr@mayo.edu.

What is/are the Locations of this Clinical Trial?

• Rochester, MN

Last updated: 07/11/2008