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Phase 2 N=44 Treatment

Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma

Neuroblastoma · Sarcoma · Rhabdomyosarcoma-Embryonal · Rhabdomyosarcoma- Alveolar · Neuroectodermal Tumors, Primitive, Peripheral

Enrolled (actual)
44
Serious AEs
56.3%
Results posted
Sep 2013
Primary outcome: Primary: Number of Participants With a Positive Immune Response as Evidenced by the Delayed Type of Hypersensitivity (DTH) Reaction Assay — 0; 15 Participants — p=0.043

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
Tumor Purged/CD25 Depleted Lymphocytes (Drug); Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine (Biological); rhIL-7 (Drug); Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine (Biological)
Age
Pediatric, Adult · 0+ yrs
Sex
All
Sponsor
National Cancer Institute (NCI)
Primary completion
Aug 2012

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants With a Positive Immune Response as Evidenced by the Delayed Type of Hypersensitivity (DTH) Reaction Assay
0; 15 0.043 sig
PRIMARY
Toxicity
6; 24
PRIMARY
Overall Survival
2.4; 4.3

Summary

Background: * Pediatric solid tumors (Ewing's sarcoma, rhabdomyosarcoma, and neuroblastoma) are often difficult to cure with standard treatment. * Immune therapy using an experimental vaccine made from proteins from the patient's tumor cells may boost the body's immune response against the tumor. * The effects of chemotherapy on the immune system can potentially make immunotherapy more effective if administered soon after completion of chemotherapy. The addition of recombinant human IL-7 (interleukin 7) (rhIL-7 (recombinant human interleukin 7)) may make the immunotherapy more effective. Objectives: -To determine whether immune therapy given after immune suppression can help the body fight the tumor and to determine the safety of the treatment. Eligibility: -Patients with solid tumors, i.e., Ewing's sarcoma, rhabdomyosarcoma or neuroblastoma whose disease has recurred after treatment or spread beyond the original site Design: * Patients undergo tumor biopsy (removal of a piece of tumor tissue) to collect tumor cells for making a vaccine from proteins in the patient's tumor and apheresis (removal of a quantity of white blood cells) to collect white cells for re-building the immune system after immune therapy. Apheresis is repeated three times during immunotherapy (weeks 8, 14 and 20). * After receiving standard chemotherapy for their tumor (and an additional course of fludarabine and cyclophosphamide to further suppress immunity if needed) patients receive immune therapy in Cohorts A and B. rhIL-7 is given 48 hours before the vaccine, as an injection under the skin in an extremity that will not be used for the vaccine in patients in Cohort B only. You will be watched closely for 6 hours after the rhIL-7 for any signs of reaction. rhIL-7 will be given before vaccine doses #1, #2, #3, and #4. The vaccine is given at study weeks 2, 4, 6, 8, 10 and 12. Each vaccine is given as a total of six separate rhIL-7 followed by injections: three intradermal (like a (tuberculosis) TB test) on one arm or leg and three subcutaneous (like those for insulin injections for diabetes). on the other arm or leg. An anesthetic cream may be used to minimize the discomfort of injections. * Patients' white cells are returned to them by infusion through a vein on the first day of immune therapy. * Imaging studies and immune studies are done at weeks 1, 8 and 20 to determine the response to treatment on the tumor and on the immune system.

Eligibility Criteria

  • INCLUSION CRITERIA: for Apheresis/Tumor biopsy portion of the trial:

A. Diagnosis

  • rhabdomyosarcoma: embryonal or alveolar.
  • Ewing's sarcoma family of tumors (ESFT), which include: classical, atypical and extraosseous ESFT, peripheral primitive neuroectodermal tumors, peripheral neuroepithelioma, primitive sarcoma of bone, and ectomesenchymoma.
  • neuroblastoma: may be diagnosed via histology or the standard clinical evidence for increased catecholamines in the urine plus tumor cells in the bone marrow.
  • undifferentiated or embryonal sarcoma.
  • desmoplastic small round cell tumor.
  • synovial cell sarcoma.

B. Extent of Disease/Previous Therapy

  • Initial presentation: Stage IV or metastatic disease, enrolled prior to any cytoreductive therapy.
  • Recurrent Disease:
  • Patient > 5yo must have recovered CD4 count to > 350 cells/mm^3 OR have disease free interval > one year from completion of cytotoxic therapy
  • Patients 350 cells/mm^3 OR have disease free interval > six months from completion of cytotoxic therapy
  • Multiple recurrences are allowable as long as CD4 count or disease-free intervals have been met.

C. Age/Weight

  • greater than 18 mos. and less than or equal to 35 years at the time of initial diagnosis.
  • greater than 10 kg at the time of apheresis. Patients between 10-15 kg must be approved by the apheresis unit prior to enrollment on protocol.

D. Informed Consent

All patients or their legal guardians (if the patient is less than 18 years old) must sign a document of informed consent (screening protocol) prior to performing studies to determine patient eligibility. After confirmation of patient eligibility all patients or their legal guardians must sign the protocol specific informed consent to document their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (other than the studies which were performed to determine patient eligibility).

E. Laboratory Parameters

  • renal function: creatinine clearance greater than 60 mL/min/1.73m^2 or normal age adjusted serum creatinine (less than or equal to 5 yrs. less than or equal to 0.8 mg/ml; 5-10 yrs. less than or equal to 1.0 mg/ml; 10-15 yrs. less than or equal to 1.2 mg/ml; greater than 15 yrs. less than or equal to 1.5 mg/ml)
  • liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5 times upper limit of normal (ULN), bilirubin less than 1.5 ULN
  • hematologic function: platelets greater than 50,000 cells/mcl, hemoglobin (Hgb) greater than 9.0 gms/dl, prothrombin time (PT) less than 1.5 ULN. Patients may receive transfusion if necessary to reach the pre-apheresis hematology parameters.

F. Accessibility of Tissue to Generate Tumor Lysates

Patients must have adequate tumor bulk accessible to biopsy in order to generate the tumor lysate (at least 2 cm diameter). Procedures employed to acquire biopsies for tumor lysates will be limited to percutaneous biopsies or open biopsies of readily accessible lesions. Patients should not undergo biopsies, which will later compromise the ability to render function preserving local therapy (e.g. limb salvage therapy). To prevent this, all bone biopsies should be performed in consultation with the orthopedic consultant on the case. For patients with bone marrow involvement, bone marrow aspirates may be used as a source of tumor for tumor lysates. Patients are not eligible if, in the opinion of the principal and associate investigators, tumor biopsy would entail extensive surgery such as thoracotomy or laparotomy, or if the tumor site places the patient at substantial risk from the biopsy procedure.

National Cancer Institute (NCI) Laboratory of Pathology will review all tumor specimens for diagnosis.

EXCLUSION CRITERIA: for Apheresis/Tumor biopsy portion of the trial:

A. Other conditions

  • Clinically significant unrelated systemic illness, such as serious infections, autoimmunity or organ dysfunction, which in the j
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00923351). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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