IRB Number:

07-007525

Trial Status:

Open for Enrollment

Phase: I

Why is this study being done?

Patients are being asked to take part in this research study because they have been diagnosed with acute lymphocytic leukemia (ALL) and have agreed to be treated on a COG treatment study. In this study, the researchers want to learn more about children who are treated on the COG studies AALL0232 and AALL0434. In both these treatment studies, patients (people on the study) are randomized (randomized means assigned randomly like the flip of a coin, but it is done by a computer so no one will know what treatment the patient will receive) between two different treatment arms that compare different ways to give the chemotherapy, methotrexate. Methotrexate is given in a two month long phase of treatment called Interim Maintenance.

In this study, the research staff want to closely evaluate side effects that might be due to methotrexate. Specifically, the researchers want to learn more about possible side effects that affect the nervous system. A recent, large study of adult survivors of childhood ALL found no differences between survivors who never received radiation treatments and the general population with respect to the likelihood of being married, having a job, and having health insurance.

However, there are children who have neurologic side effects during therapy, or who have learning disabilities after therapy has ended. This study is looking at whether the use of methotrexate is likely to cause those side effects that affect the nervous system. This study will also look at whether or not the possible side effects are different with the different ways methotrexate is given.


Why Is This Study Being Done?
The study is being done to determine the effects, if any, of methotrexate, on learning skills and memory. Information gathered from previous studies is incomplete. There is currently no way of predicting who is likely to develop nervous system side effects related to the use of methotrexate, regardless of the way that methotrexate is given. Side effects are unintended or unwanted results of treatment. In addition, there is no way of predicting whether the nervous system side effects will be minor or major.

This study will also determine: 1) Whether rare, sudden side effects of leukemia therapy, such as seizures, are associated with learning difficulties; 2) Whether certain genetic traits (qualities of a person?s DNA that make the person unique) are associated with the possibility of methotrexate side effects; 3) Whether changes in the amounts of a substance that is found in the patient?s body are associated with side effects of methotrexate, and; 4) Whether or not a new imaging study, similar to an MRI, will predict who is at risk for side effects related to methotrexate.

The overall goal of this study is to evaluate the potential toxicity associated with methotrexate in more detail.

Who is Eligible to Participate in the Study?

-At least 1 year old and less than 18 years of age
-Diagnosed with acute lymphocytic leukemia (ALL)
-Patient must NOT have any of the following:
o Presence of a known significant neurodevelopmental disability unrelated to the cancer diagnosis (e.g., Down's Syndrome, Fragile X mental retardation, autism, pervasive
developmental disability, pre-existing seizure disorder). Children with a prior history of attention deficit hyperactivity disorder or a specific learning disability (e.g., dyslexia) are eligible for this study.
o or sensory impairment (e.g., pre-existing uncorrectable vision impairment or deafness).
o CNS-3 disease at diagnosis nor be scheduled to receive cranial radiation therapy (CRT).

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

What is Involved With this Study?

Neurocognitive Testing
If choosing to participate in this study, patients will be asked to undergo three different assessments that measure thinking, memory, attention and concentration. There
will not be a charge for these tests. The first test would take place as soon as it is clear that the patient's therapy will not include radiation treatment to the brain. The final decision about the use of radiation is usually made within one week of completing the first four week phase of treatment, called Induction. The second test would occur approximately one year later, as the patient enters the maintenance phase of therapy, and the third test would take place one year following the completion of all therapy.

These are paper and pencil tests. They may also include puzzles and various other tests of problem solving. There are no physical risks involved. Patients may become tired and/or frustrated. There will be breaks and snacks and if the patient cannot continue with a particular examination, then that session will end. Each of the three tests sessions will require approximately 3½ hours. The results of these studies will be made available to the patient.

If a psychologist is not available at the patient's institution to perform the neurocognitive assessments, the patient may choose to travel to the closest institution, with an available psychologist, to have the neurocognitive assessments performed. Travel costs will be paid by COG.

Blood and Spinal Fluid Collections
Patients will be asked to allow for the collection of three blood samples and one spinal fluid sample over the 2 1/3 to 3 1/3 years of leukemia treatment. These samples would be used to measure quantities of normal compounds that may change in response to methotrexate.

Another blood sample, drawn when the patient's leukemia was diagnosed, will be used to look at how naturally occurring differences in genes (polymorphisms) might play a role in why some people may develop side effects when treated with methotrexate.

The spinal fluid sample (about a teaspoonful) and two of the three blood samples will be obtained at the same time as samples needed for standard patient care. One of the blood samples (1½ teaspoons that can be drawn from a line or portacath) may be drawn at a separate time.

MRI Scans
During the later phase of the study, the research staff may also ask the patient to have three imaging studies of the brain. These are MRI scan studies. MRI scans use magnetic waves to create an image. They do not involve the administration of x-ray radiation, as for example, with a CT scan. These imaging studies are not available at all institutions, so the patient will be told whether this portion of the study is being done and whether their hospital is participating in the imaging part at the time the patient is consented for this study. The doctor may ask the patient again about these studies if the imaging studies become available to the patient later during the study.

In addition to the usual MRI, diffusion tensor imaging would be performed. Diffusion tensor imaging (DTI) is a new way to create different images (pictures). There is no
difference between the procedure involved in a standard MRI and the diffusion tensor imagining. The addition of the diffusion tensor imaging adds to the time it takes to
complete the MRI by an additional 15-20 minutes. These studies would be done at around the same time as the neurocognitive testing described above. The results of the MRI will be made available to the patient. There will be no charge to the patient or their insurance company for these studies.

How long will the Study run?

The neurocognitive tests will start during the beginning of the patient's leukemia treatment. The second set of tests will be given one year after the first set of tests. The third and last set of tests will be given approximately one year after the completion of leukemia treatment therapy. The one spinal fluid sample and three blood samples would all be obtained during the Interim Maintenance phase of therapy. Should the MRI portion of the study be available, the MRIs would be done at approximately the same times as the neurocognitive tests.

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

Study Activation/Registration Date: 03/20/2008

IRB Review and Approval Date: 01/31/2008

Study Type: Symptom Management

Projected Accrual: The plan is to have up to 450 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: 05/13/2008