NIH Clinical Research Studies

Protocol Number: 07-C-0206

Active Accrual, Protocols Recruiting New Patients

Title:
A Pilot Study of Tumor Vaccination in Patients with High Risk Pediatric Solid Tumors and Altered T Cell Homeostasis
Number:
07-C-0206
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.

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 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. The vaccine is given at study weeks 2, 4, 6, 8, 10 and 12. Each vaccine is given as a total of six separate injections: three intradermal (like a 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.

Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:
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.

-Late recurrence: Completed all cytotoxic therapy greater than or equal to one year prior to recurrence for patients who are greater than 5 years of age, or completed all cytotoxic therapy greater than 6 months prior to recurrence for patients who are less than or equal to 5 years of age. Multiple recurrences are allowable as long as these treatment-free intervals have been met. At least 4 weeks must have elapsed since last dose of non-cytotoxic therapies (i.e. Avastin, monoclonal antibodies such as anti-IgF1R and anti-TRIAL, immunotherapies, etc.)

C. Age/Weight

-greater than 18 mos. and less than or qual 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 25 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: AST and ALT less than 2.5 times ULN, bilirubin less than 1.5 ULN

-hematologic function: platelets greater than 75,000 cells/mcl, Hgb greater than 9.0 gms/dl, 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 a substantial risk from the biopsy procedure.

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 judgment of the Principal or Associate Investigators would compromise the patient's ability to tolerate the investigational agents or are likely to interfere with the study procedures or results.

-Previous allogeneic stem cell or allogeneic bone marrow transplantation.

-Conditions related to tumor, which require emergency treatment (airway compression, spinal cord compression) since enrollment would delay initiation of such therapy.

-Women who are pregnant or lactating.

-Corticosteroids initiated at the time of tumor diagnosis or recurrence for treatment of nerve compression or other symptoms is permitted during this phase of the trial, but will not be permitted during the immunotherapy phase, with the exception of a self limited course of steroids as described in Section 2.1.4.A.

-Patients with a history of CNS metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidenced by stable clinical findings and stable radiographic findings for a period of 6 weeks.

Patients with human immunodeficiency virus infection, hepatitis B, or hepatitis C due to confounding effects on immune system.

Inclusion Criteria for Immunotherapy portion of the trial:

A. Informed Consent

Because significant time will have elapsed between apheresis/tumor biopsy and the initiation of immunotherapy, all patients or their legal guardians (if the patient is less than 18 years old) must sign a second 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).

B. Time and Recovery from Cytotoxic Therapy

At least 3 weeks should have elapsed since the last cycle of cytotoxic therapy or since the last dose of radiation therapy, at least 4 weeks must have elapsed since the patient has received any investigational therapy, and patients should have recovered from toxic side effects of previous therapy to a grade 1 or less, with the exception of the following:

-Hematological toxicity: recovery to levels required in Section 2.1.1.E.

-Low electrolyte levels (Such individuals should receive appropriate supplementation).

-For patients on anticoagulant therapy or with pre-existing coagulation abnormalities, PT, PTT must return to baseline.

-Liver function tests must resolve to values required in Section 2.1.1.E.

-Grade 3 hypoalbuminemia.

-Alopecia.

-Sterility.

C. Laboratory Parameters

-renal function: creatinine clearance greate 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: AST and ALT less than 2.5 times ULN, bilirubin less than 1.5 ULN.

-hematologic function: ANC greater than 750 cells/mcl, platelets greater than 75,000 cells/mcl.

D. Birth Control

Subjects of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while they are being treated on this study.

Exclusion Criteria for Immunotherapy Portion of the Trial:

A. Other conditions

-Clinically significant unrelated systemic illness, such as serious infections or organ dysfunction, which in the judgment of the Principal or Associate Investigators would compromise the patient's ability to tolerate the investigational agents or are likely to interfere with the study procedures or results.

-Persistent or progressive cancer following the completion of the standard therapy phase of the trial will not, in and of itself, preclude receipt of immunotherapy. However, patients will not receive immunotherapy if they have an ECOG performance status performance status of 3 or 4 or, for children less than or equal to 10 years of age, Lansky less than or equal to 50 (Appendix III). Furthermore, patients will be removed from the trial if they develop requirements for anti-neoplastic therapy (e.g. radiation therapy) for progressive disease during the trial as discussed in Section 3.8.

-Women who are pregnant or lactating.

-Patients with human immunodeficiency virus infection, hepatitis B, or hepatitis C infection due to confounding effects on immune function.

-Patients who require chronic daily oral corticosteroid or other immunosuppressive therapy. Topical or inhaled corticosteroids are permitted. Also, a time limited course of steroids does for an unrelated medical condition (e.g. allergic reaction, poison ivy) will not preclude receipt of immunotherapy provided that two weeks elapse between the last dose of systemic corticosteroids and initiation of immunotherapy.

-Patients who are receiving other biologic therapies including cytokines or growth factors not specified by the protocol. Herbal supplements will not result in exclusion but should be noted and reviewed with the PI.

-Patients with a history of CNS metastases from cancer are not excluded provided that the metastatic CNS disease has been effectively treated and there is no evidence of active CNS disease as evidenced by stable clinical findings and stable radiographic findings for a period of 6 weeks.

Special Instructions:
Currently Not Provided
Keywords:
Vaccine
Immunotherapy
Cancer
Chemotherapy
Ewings Sarcoma
Recruitment Keyword(s):
Cancer
Neuroblastoma
Ewing's Sarcoma
Rhabdomyosarcoma
Condition(s):
Neuroblastoma
Sarcoma
Rhabdomyosarcoma-Embryonal
Rhabdomyosarcoma- Alveolar
Neuroectodermal Tumors, Primitive, Peripheral
Investigational Drug(s):
Tumor Purged/CD25 Depleted Lymphocytes
IL-4
Investigational Device(s):
None
Intervention(s):
Drug: Tumor Purged/CD25 Depleted Lymphocytes
Biological/Vaccine: Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine
Drug: IL-4
Supporting Site:
National Cancer Institute

Contact(s):
NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):
Arndt CA, Crist WM. Common musculoskeletal tumors of childhood and adolescence. N Engl J Med. 1999 Jul 29;341(5):342-52. Review. No abstract available.

La TH, Meyers PA, Wexler LH, Alektiar KM, Healey JH, Laquaglia MP, Boland PJ, Wolden SL. Radiation therapy for Ewing's sarcoma: results from Memorial Sloan-Kettering in the modern era. Int J Radiat Oncol Biol Phys. 2006 Feb 1;64(2):544-50. Epub 2005 Sep 28.

Barker LM, Pendergrass TW, Sanders JE, Hawkins DS. Survival after recurrence of Ewing's sarcoma family of tumors. J Clin Oncol. 2005 Jul 1;23(19):4354-62. Epub 2005 Mar 21.

Active Accrual, Protocols Recruiting New Patients

If you have:


Command Menu Bar

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home


Clinical Center LogoNational Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 09/16/2008
Search The Studies Help Questions