IRB Number:

962-05

Trial Status:

Open for Enrollment

Phase: I

Why is this study being done?

This study is being done to see if stronger chemotherapy (anti-cancer drugs) used with less radiation therapy can bring about a remission (make the cancer go away).
Patients are being asked to take part in this study because they have acute lymphoblastic leukemia (ALL). At least 18 months have passed since they were first diagnosed with ALL. The leukemia had gone away (been in remission) but now it has returned (relapsed). The leukemia returned in their central nervous system (brain and spinal cord) and the testes.
The research staff know that radiation therapy can cause long-term side effects (side effects are unintended physical reactions to the drugs that are unrelated to the reasons the drugs are being used). The researchers hope to find out if this study treatment will still make the same high rates of remission that are seen with standard treatment but cause less long-term side effects. In addition to these treatment aims, the research staff would like to use information collected on this study to answer some research questions that might help future patients. Patients can choose to be on this clinical trial without taking part in this piece of the research.

The research aims are as follows:
- See if tiny amounts of leukemia cells might be present in the bone marrow (the soft tissue in the hollow of flat bones of the body that makes new blood cells) at the time of relapse (study entry). Researchers want to know if the amount of these cells can tell the research staff how well a patient might respond to treatment.
- Look for changes in the genetic structure (DNA) of relapsed patients. The research staff want to see if genetic changes make a difference in how the patient responds to treatment and in the types of side effects the patient has while being treated.
- Look at the effects that the disease and treatment have on thinking, learning, and behavior. The research staff want to know if patients have fewer learning and other psychological problems if less CNS radiation therapy is given.

Who is Eligible to Participate in the Study?

-Ages 18 months to 29 years old
-Diagnosis of acute lymphoblastic leukemia (ALL)
-First isolated CNS and/or testicular relapse
-No prior bone marrow transplantation

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

What is Involved With this Study?

All patients receive common induction, consolidation, re-induction, and intensification chemotherapy. Patients are stratified to maintenance therapy according to site of extramedullary relapse (CNS vs testicular).
- Induction therapy (weeks 1-4): Patients receive vincristine IV on days 1, 8, 15, and 22; oral dexamethasone twice daily on days 1-28; daunorubicin* IV over 15 minutes on days 1, 8, and 15; and intrathecal triple therapy** (ITT) comprising methotrexate, hydrocortisone, and cytarabine on days 1, 8, 15, and 22.

NOTE: *The total dose of anthracyclines on this study is capped at 450 mg/m2. Once this dose is reached, all subsequent doses of daunorubicin are omitted.

NOTE: **Patients with isolated testicular relapse receive ITT on day 1 only.

In addition to the above, patients with isolated testicular relapse also receive high-dose methotrexate IV continuously over 24 hours on day -14. Patients with clinical signs of disease at the end of induction undergo testicular biopsy.
Patients with CNS disease who do not achieve CNS remission after induction therapy receive additional ITT as above on days 29 and 36.

- Consolidation therapy (weeks 5-10): Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-2 and 22-23 and pegaspargase intramuscularly (IM) on days 2 and 23. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on days 3 and 24 and continuing until blood counts recover.

Patients with isolated testicular relapse with positive biopsy results at the end of induction undergo testicular radiotherapy once daily for a total of 12 fractions during consolidation therapy.

- Intensification I (weeks 11-22): Patients receive high-dose methotrexate with leucovorin calcium rescue IV over 24 hours on days 1, 22, 43, and 64 and oral mercaptopurine once daily on days 2-6, 23-27, 44-48, and 65-69. Patients also receive etoposide IV over 1 hour and cyclophosphomide IV over 15-30 minutes on days 8, 29, 50, and 71. Patients receive ITT* on days 15, 36, 57, and 78.

NOTE: *Patients with isolated testicular relapse receive ITT on days 36 and 78 only.

- Reinduction therapy (weeks 23-26): Patients receive vincristine IV on days 1, 8, 15, and 22; oral dexamethasone twice daily on days 1-28 (for patients < 13 years of age) OR twice daily on days 1-7 and 15-21 (for patients ≥ 13 years of age); and daunorubicin IV over 15 minutes on days 1, 8, and 15.

- Intensification II (weeks 27-50): Patients receive high-dose cytarabine IV over 3 hours twice daily on days 1-2, 43-44, 85-86, and 127-128; pegaspargase IM on days 2, 44, 86, and 128; ITT* on days 22, 64, 106, and 148; high-dose methotrexate IV continuously over 24 hours on days 29, 71, 113, and 155; oral mercaptopurine on days 30-34, 72-76, 114-118, and 156-160; and etoposide IV over 1 hour and cyclophosphamide IV over 15-30 minutes on days 36, 78, 120, and 162. Patients also receive G-CSF SC beginning on days 3, 45, 87, and 129 and continuing until blood counts recover.

NOTE: *Patients with isolated testicular relapse receive ITT on days 22 and 106 only.

- Chemotherapy and radiotherapy (weeks 51-54): Patients receive dexamethasone orally or IV twice daily on days 1-21 (for patients < 13 years of age) OR on days 1-7 and 15-21 (for patients ≥ 13 years of age). Patients also receive vincristine IV on days 1, 8, and 15 and pegaspargase IM on days 1 and 15.

Patients with isolated CNS relapse also undergo cranial radiotherapy once daily, 5 days a week, for a total of 8 fractions.

- Maintenance therapy for isolated CNS relapse: (weeks 55-104): Patients receive dexamethasone orally or IV twice daily on days 1-5; oral mercaptopurine once daily on days 1-42; methotrexate IM on days 1, 8, 15, 22, 29, and 36; and vincristine IV and cyclophosphomide IV over 1 hour on days 43, 50, 57, and 64. Treatment repeats every 10 weeks for 5 courses.

Maintenance therapy for isolated testicular relapse:

- (Weeks 55-74): Patients receive ITT on day 1 and dexamethasone, mercaptopurine, methotrexate, vincristine, and cyclophosphomide as in maintenance therapy for isolated CNS relapse. Treatment repeats every 10 weeks for 2 courses.

- (Weeks 75-106): Patients receive vincristine IV on day 1; dexamethasone orally or IV on days 1-5; oral mercaptopurine on days 1-28; and methotrexate IM on days 1, 8, 15, and 22. Treatment repeats every 28 days for 8 courses. Patients also receive ITT on day 1 every 12 weeks for 3 doses.

Patients with combined testicular and CNS relapse receive high-dose methotrexate IV continuously over 24 hours on day -14 in addition to the same chemotherapy and radiotherapy administered during the induction, consolidation, intensification I, reinduction, intensification II, and maintenance phases of therapy as isolated CNS relapse patients.

All patients undergo neuropsychological assessment within three months after completion of induction therapy (before cranial radiotherapy) and at two years after completion of treatment.

How long will the Study run?

Patients will be in the study for about two years. However, they will continue to have physical exams and blood tests for years after treatment. The research staff would like to continue to find out about their health for about five years after the study closes to new patients. Keeping in touch with the patient and checking on how their health is every year for a while after the study closes helps researchers to understand the long-term effects of the study.

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

Study Activation/Registration Date: 08/22/2005

IRB Review and Approval Date: 07/14/2005

Study Type: Treatment

Projected Accrual: The plan is to have up to 198 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: 05/14/2008