Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) in High Risk Ewing's Sarcoma Patients
Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) in High Risk Ewing's Sarcoma Patients
Objectives:

 1. To determine if dose intensive Vincristine, Doxorubicin, Cyclophosphamide and
 Dexrazoxane (VACdxr) with or without ImmTherTM can improve the 2-year disease-free
 survival seen with standard VAC therapy.

 2. To evaluate the feasibility and describe the toxicity associated with VACdxr.

 3. To evaluate the feasibility and describe the toxicity of administering ImmTherTM on a
 weekly basis for 50- 52 weeks.

 4. To determine which therapy (VACdxr+ or VACdxr-) is worthy of further evaluation.
Patients will be assigned at random (as by the toss of a coin) to receive 1 of 2 treatments.

 Arm A: VACdxr will be given over 2 days through a needle in a vein. On day 1, vincristine
 will be given over 15 minutes, and doxorubicin will be given over 30 minutes.

 Dexrazoxane will be given 30 minutes before doxorubicin; this drug protects the heart from
 damage by doxorubicin. Cyclophosphamide will be given once a day on days 1 and 2. This will
 make up 1 cycle of VACdxr treatment; the cycle will be repeated every 3 weeks for up to 6
 cycles.

 To prevent some side effects of VACdxr, the drugs Mesna and Neupogen/or Neulasta will also be
 given. Mesna helps prevent bladder damage. Neupogen is a growth factor that stimulates the
 body to make more white blood cells. Neulasta is a growth factor related to Neupogen.

 After cycle 3, surgery may be done to remove any tumor that remains. The principal
 investigator will also decide whether radiation treatment should be done. If so, patients
 will receive radiation therapy.

 Starting 1 month after all treatment is done, patients will receive ImmTher. ImmTher
 stimulates the body's white blood cells to attack and kill tumor cells. The drug will be
 given through a needle in a vein over 1 hour, every week for 1 year.

 Arm B: Patients will be treated the same as patients in Arm A, except that they will not
 receive ImmTher.

 Patients may have to stay in the hospital during VACdxr treatment and after surgery. Patients
 will receive ImmTher in the outpatient clinic.

 Before treatment starts, patients will have a complete exam including blood and urine tests
 and an EKG and ECHO or multiple gated acquisition scan (MUGA) (heart function tests). X-rays
 and CT, MRI, bone marrow aspiration, and bone scans will be done. Women will have a pregnancy
 test.

 After each treatment with drugs, after surgery, and after radiation treatment, patients will
 have checkups. These will include blood and urine tests and sometimes x-rays.

 After cycle 3 of VACdxr, patients will have chest x-ray and x-ray of primary tumor. CT chest,
 MRI, bone marrow aspiration and bone scans will be done after 3 cycles as indicated. These
 tests will be done to record and measure tumors.

 After treatment stops, patients will return for checkups every 3 months for 2 years.

 This is an investigational study. ImmTher is an investigational agent. All other study drugs
 are approved by the U.S. Food and Drug Administration. As many as 104 patients will take part
 in the study; about 95 of these will be treated at M.D. Anderson.
Inclusion Criteria:

 -  High risk Ewing's Family of tumors (metastatic disease at diagnosis, humerus, femur or
 trunk primary, bulky primary (greater than 8 cm)), or LDH greater or equal to 900
 IU/ml prior to biopsy.

 -  No prior chemotherapy.

 -  Written informed consent

 -  Normal cardiac function (ejection fraction greater or equal to 50%).

 -  Males and non pregnant females.

 -  Biologic age 3-60 years old.

 -  Adequate bone marrow function (defined as an absolute peripheral granulocyte count
 of>500/mm3, platelet count of >75,000/mm3, and hemoglobin >8g/dl with transfusion if
 required).

 -  Adequate renal function defined as blood urea nitrogen (BUN) <30mg% and serum
 creatinine <1.5 x normal for age or creatinine clearance >70.

 -  Patients of child bearing potential must agree to use an effective method of
 contraception.

 -  Normal hepatic function (bilirubin <1.5mg/dl, serum glutamate oxaloacetate
 transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) <3x normal).

 Exclusion Criteria: N/A