Therapy to Treat Ewing's Sarcoma, Rhabdomyosarcoma or Neuroblastoma
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|ClinicalTrials.gov Identifier: NCT00923351|
Recruitment Status : Completed
First Posted : June 18, 2009
Results First Posted : September 20, 2013
Last Update Posted : June 15, 2018
- 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.
-To determine whether immune therapy given after immune suppression can help the body fight the tumor and to determine the safety of the treatment.
-Patients with solid tumors, i.e., Ewing's sarcoma, rhabdomyosarcoma or neuroblastoma whose disease has recurred after treatment or spread beyond the original site
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma Sarcoma Rhabdomyosarcoma-Embryonal Rhabdomyosarcoma- Alveolar Neuroectodermal Tumors, Primitive, Peripheral||Drug: Tumor Purged/CD25 Depleted Lymphocytes Biological: Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine Drug: rhIL-7 Biological: Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine||Phase 1 Phase 2|
- Patients with recurrent or metastatic pediatric solid tumors experience low survival rates, but using current standard therapies, many patients with these diseases are rendered into a state of minimal residual disease associated with lymphopenia.
- Lymphopenic hosts show augmented immune reactivity, which may be favorable for inducing antitumor immune responses.
- To determine whether Alpha cluster of differentiation 25 (CD25) and 8H9 depleted autologous lymphocytes plus tumor lysate/keyhole limpet hemocyanin (KLH) pulsed dendritic cell vaccines plus or minus r-hIL7 (CYT107) can induce immune responses to tumor lysate in this patient population rendered lymphopenic by cytotoxic therapy.
- To assess the safety of administering lymphocytes depleted of cluster of differentiation 4 (CD4) plus CD25plus suppressor T cells plus or minus r-hIL (CYT107 (interleukin 7)) to lymphopenic hosts.
- Patients with metastatic or recurrent pediatric solid tumors of the following histologies: Ewing's sarcoma family of tumors, rhabdomyosarcoma or neuroblastoma, synovial cell sarcoma, desmoplastic small round cell tumor, undifferentiated sarcoma, embryonal sarcoma.
- Patients must have sufficient accessible tumor for biopsy to generate tumor lysate.
- Patients must meet eligibility criteria upon enrollment and upon completion of standard therapy prior to administration of immunotherapy as significant time will have elapsed between the time points.
- Immunotherapy consists of one autologous lymphocyte infusion depleted of CD25plus suppressive T cells and depleted of contaminating tumor cells plus 6 sequential tumor lysate/KLH pulsed dendritic cell vaccines. No cytokine is administered on Arm A and r-hIL7 (CYT107) is administered on Arm B.
- Patients will be evaluated for immune responses to tumor lysates using ex vivo assays and delayed type hypersensitivity (DTH).
- The trial uses a one-stage design targeting a response rate of 50 percent. Up to 47 patients will be treated.
- Stopping rules will take effect if excessive toxicity is observed.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||44 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Tumor Vaccination and R-hIL-7 Following Standard Multimodality Therapy in Patients With High Risk Pediatric Solid Tumors|
|Actual Study Start Date :||June 2, 2007|
|Actual Primary Completion Date :||August 30, 2012|
|Actual Study Completion Date :||May 15, 2018|
Experimental: Arm A - Participants who did not receive rhIL-7
Six patients with Ewings sarcoma family or tumors (ESFT) participants will receive cytotoxic/lympholytic therapy with cyclophosphamide and fludarabine (if cluster of differentiation 4 (CD4) count > 200 cells/mcl). Participant will receive Tumor lysate/keyhole limpet hemocyanin (KLH) pulsed dendritic cell vaccine followed by Infusion of 8H9/CD25 depleted autologous lymphocyte infusion on Day 1, followed by Tumor lysate/KLH pulsed dendritic cell vaccine on week 4, 6, 8, 10, and 12.
Drug: Tumor Purged/CD25 Depleted Lymphocytes
Experimental: Arm B - Participants who received rhIL-7
Eight patients with rhabdomyosarcoma, fifteen patients with Ewings sarcoma family or tumors (ESFT), two patients with desmoplastic small round cell tumor, and one patient with synovial cell sarcoma participants will receive CYT107 20 mcg/kg/dose subcutaneous (SQ) (approx. 48h prior to vaccine[Day 0]), Tumor lysate/KLH pulsed dendritic cell vaccine followed by Infuse 8H9/CD25 depleted autologous lymphocyte infusion on Day 2, followed by CYT107 20 mcg/kg/dose SQ on days 14, 28 and 42 (± 7 days), and Tumor lysate/KLH pulsed dendritic cell vaccine on Days 16, 30, 44, 56, and 70 (± 7 days).
Apheresis/flow cytometry/delayed type of hypersensitivity (DTH) responses for immune endpoint monitoring (skin tests) will be performed on Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (+/- 7 days) (Arm B); and radiographic studies for clinical restaging will be performed on Week 8 and 20 (Arm A) and Days 42 and 126 (+/- 7 days) (Arm B).
Biological: Tumor Purged/CD25 Depleted Lymphocytes with Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine
Tumor lysate/KLH pulsed dendritic cells (minimum of 1 X 10e6 cells/kg) on Day2.
rhIL-7 (20 mcg/kg/dose SQ) approx. 48 hours prior to vaccine) Day 0, Day 14, Day 28 and Day 42
Biological: Tumor Lysate/KLH Pulsed Dendritic Cell Vaccine
Tumor lysate/KLH Pulsed dendritic cell vaccine (1-5 X 10e7 cells/injection site, given in 3 sites intradermal) on Day 2, Day 16, Day 30, Day 44, Day 56, Day 70.
- Number of Participants With a Positive Immune Response as Evidenced by the Delayed Type of Hypersensitivity (DTH) Reaction Assay [ Time Frame: Week 8, 14, 20 (Arm A) and on Days 42, 84 and 126 (± 7 days) (Arm B) ]
A positive response to the tumor vaccine requires a positive reaction in at least one of the two assays below (immune responses to tumor lysates using ex vivo and delayed type of hypersensitivity (DTH).
The presence of a positive delayed type of hypersensitivity (DTH) reaction to the tumor lysate in a patient who did not show a positive DTH reaction prior to immunotherapy. A positive reaction is induration of at least 0.5 cm.
Immunotherapy administered to patients with recurrent or metastatic pediatric solid tumors such as Ewing's sarcoma, rhabdomyosarcoma, or neuroblastoma. Each vaccine is given as 6 separate injections. Three intradermal on one arm or leg and three subcutaneous on the other arm or leg.
- Toxicity [ Time Frame: Date treatment consent signed to date off study, approximately 49.5 months ]Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
- Overall Survival [ Time Frame: Time between the first day of treatment to the day of death or at the conclusion of 5 years of follow-up, whichever comes first, assessed up to approximately 11 years. ]Overall survival is defined as the time between the first day of treatment to the day of death.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00923351
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||John Glod, M.D.||National Cancer Institute (NCI)|