• Feasibility [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]
• Graft-versus-tumor effects [ Designated as safety issue: No ]

• Feasibility
• Toxicity
• Graft-versus-tumor effects

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: This phase II trial is studying combination chemotherapy and donor peripheral stem cell transplantation to see how well they work in treating young patients with recurrent sarcoma.

OBJECTIVES:

Primary

• Determine the percentage of patients with high-risk, recurrent pediatric sarcoma who achieve full donor engraftment by day 100 after treatment with induction chemotherapy followed by allogeneic/syngeneic peripheral blood stem cell transplantation.
• Determine the toxic effects of this regimen in these patients.
• Determine the incidence of graft-vs-host disease (GVHD) and the immune reconstitution rate in patients treated with this regimen.
• Determine whether allogeneic graft-vs-tumor responses after this regimen can induce clinically significant anti-tumor effects in these patients.
• Correlate evidence of increased thymic metabolic activity on fludeoxyglucose F 18 (FDG) positron-emission tomography (PET) scanning with immune reconstitution parameters in patients treated with this regimen.
• Evaluate FDG-PET scanning as a measure of disease activity in these patients by correlation with standard radiologic modalities and clinical outcome.

Secondary

• Evaluate the use of sirolimus and abbreviated tacrolimus as GVHD prophylaxis in these patients.

OUTLINE:

• Induction Chemotherapy: Patients receive induction chemotherapy comprising fludarabine IV over 30 minutes on days 1-3; etoposide IV continuously, doxorubicin IV continuously, and vincristine IV continuously on days 1-4; cyclophosphamide IV over 30 minutes on day 5; oral prednisone on days 1-5; and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days (until CD4 count is less than 50/mm^3) for up to 3 courses in the absence of disease progression or unacceptable toxicity.
• Preparative Regimen: Beginning 22 days after the last course of induction chemotherapy, patients begin the transplantation preparative regimen. Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 2 hours on days -6 to -3 and melphalan IV over 15 minutes on day -2. Allogeneic peripheral blood stem cells are infused on day 0. Patients then receive G-CSF SC beginning on day 0 and continuing until blood counts recover.
• Graft-vs-host disease (GVHD) prophylaxis (first 17 patients [closed to accrual as of 4/9/05]): Patients receive GVHD prophylaxis comprising cyclosporine IV over 2 hours every 12 hours beginning on day -1. Once oral feedings are tolerated, patients receive oral cyclosporine every 12 hours until day 28 (possibly longer if GVHD develops) followed by a taper over 2-4 weeks.* NOTE: *Patients with a genotypically identical twin stem cell donor do not receive GVHD prophylaxis
• GVHD prophylaxis (additional patients): Patients receive GVHD prophylaxis comprising tacrolimus IV or orally beginning on day -1 and continuing for at least 28 days and oral sirolimus beginning on day 3 and continuing for approximately 100 days.
• Lymphocyte Infusion: Approximately 28 days post-transplantation, patients receive 3 donor lymphocyte infusions every 2-4 weeks provided there has been no evidence of GVHD. Patients with persistent or progressive disease may receive adjuvant chemotherapy with standard disease-specific agents or be taken off study.

Patients are followed 1-2 times weekly for the first 100 days post-transplantation, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

• Biological: filgrastim
• Biological: therapeutic allogeneic lymphocytes
• Drug: cyclophosphamide
• Drug: cyclosporine
• Drug: doxorubicin hydrochloride
• Drug: etoposide
• Drug: fludarabine phosphate
• Drug: melphalan
• Drug: prednisone
• Drug: sirolimus
• Drug: tacrolimus
• Drug: vincristine sulfate
• Procedure: peripheral blood stem cell transplantation

DISEASE CHARACTERISTICS:

• Diagnosis of one of the following pediatric sarcomas:

  • Ewing's sarcoma family of tumors or alveolar rhabdomyosarcoma with at least one of the following characteristics:

    • Macrometastatic disease at initial diagnosis provided patient is enrolled after completion of standard front-line therapy comprising the following agents:

      • Vincristine, cyclophosphamide, doxorubicin, ifosfamide, and etoposide for Ewing's sarcoma family of tumors
      • Vincristine, cyclophosphamide, dactinomycin, and/or doxorubicin for alveolar rhabdomyosarcoma
    • Recurrent disease at any site less than 1 year after completing standard front-line therapy or second or subsequent recurrence at any time after completing standard front-line therapy
    • Progressive disease while receiving standard front-line chemotherapy

  • Desmoplastic small round cell tumor

    • Completed front-line standard therapy comprising vincristine, cyclophosphamide, and doxorubicin

    • Meets any of the following criteria:

      • Unresectable disease
      • Metastatic tumor (abdominal and extra-abdominal disease)
      • Progressive disease while receiving standard therapy
      • Recurrence within 1 year of completing therapy

• 5/6 or 6/6 HLA-matched first-degree sibling donor available

  • Single HLA-A or B locus mismatch is allowed
  • Genotypically identical twin-match allowed

• No prior CNS tumor involvement

  • Extradural masses that have not invaded the brain parenchyma or parameningeal tumors without evidence of leptomeningeal spread are allowed

PATIENT CHARACTERISTICS:

Age

• 4 to 35

Performance status

• ECOG 0-2 OR
• Lansky 60-100% (age 10 and under)

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count greater than 750/mm^3*
• Platelet count at least 75,000/mm^3* (transfusion independent)
• Lymphopenia, CD4 lymphopenia, leukopenia, or anemia allowed
• No Fanconi's anemia NOTE: *Unless due to underlying disease

Hepatic

• Bilirubin less than 2 mg/dL
• AST and ALT no greater than 2.5 times upper limit of normal
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative
• No chronic active hepatitis (even if treated)

Renal

• Creatinine adjusted according to age as follows:

  • 0.8 mg/dL (4-5 years)
  • 1.0 mg/dL (6-10 years)
  • 1.2 mg/dL (11-15 years)
  • 1.5 mg/dL (16 and over) OR
• Creatinine clearance at least 60 mL/min

Cardiovascular

• LVEF at least 45% by MUGA or ≥ 55% by echocardiogram (ECHO) OR
• Fractional shortening at least 28% by ECHO

Pulmonary

• DLCO at least 50% of predicted corrected for alveolar volume

Other

• No uncontrolled fungal infection
• No high risk of inability to comply with protocol or give informed consent
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior autologous stem cell rescue after high-dose chemotherapy allowed

Chemotherapy

• See Disease Characteristics
• See Biologic therapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No concurrent enrollment on another clinical trial for treatment of progressive disease