A Phase I/II Study Of Immunization With Lymphotactin And Interleukin 2 Gene Modified Neuroblastoma Tumor Cells (CHESAT)
The investigators intend to test the safety, and immunologic and clinical efficacy of a combination of 2 allogeneic neuroblastoma tumor cell line vaccines, one of which has been genetically modified to secrete the cytokine/chemokine combination of IL-2 and lymphotactin, in patients undergoing chemotherapy for newly diagnosed, high risk neuroblastoma who receive single autologous stem cell rescue as consolidation therapy.
This protocol will be carried out as a Phase I/IIa study to evaluate the safety and toxicity of adding a previously unstudied, unmodified, irradiated neuroblastoma cell line (SKNLP) to a studied, safe dose of a gene modified, IL-2/Lptn secreting neuroblastoma cell line SJNB-JF-IL2/Lptn to be given as a vaccine to patients diagnosed with high risk neuroblastoma.
|Neuroblastoma||Biological: SJNB-JF-IL2 and SJNB-JF-Lptn vaccine Biological: SKNLP Vaccine||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study Of Immunization With Lymphotactin And Interleukin 2 Gene Modified Neuroblastoma Tumor Cells After High-Dose Chemotherapy And Autologous Stem Cell Rescue In Patients With High Risk Neuroblastoma|
- Evaluate the safety of repeated immunization with gene-modified, IL-2/lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-Lptn cells co-administered with the unmodified SKNLP neuroblastoma cell line. [ Time Frame: 1 year ]
- Evaluate the immune response to these immunizations. [ Time Frame: 1 year ]
- Estimate 3 year progression free survival (PFS) in vaccinated patients. [ Time Frame: 3 years ]
- Estimate 3 year overall survival (OS) in vaccinated patients. [ Time Frame: 3 years ]
- Evaluate changes in minimal residual disease load by polymerase chain reaction pre- and post-vaccination. [ Time Frame: 1 year ]
|Study Start Date:||June 2008|
|Estimated Study Completion Date:||May 2024|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
Experimental: Neuroblastoma vaccine
SJNB-JF-IL2 and SJNB-JF-Lptn vaccine and SKNLP vaccine
Biological: SJNB-JF-IL2 and SJNB-JF-Lptn vaccine
Biological: SKNLP Vaccine
*SJNB-JF-IL2 and SJNB-JF-Lptn cells are each dosed at 1x10e7 cells/m2/vaccination. This will be given in conjunction with an escalating dose of SKNLP vaccine.
Dose Level 1: 1x10e6 cells/m2/vaccination
Dose Level 2: 1x10e7 cells/m2/vaccination
TREATMENT PLAN: Standard Chemotherapy for Neuroblastoma: Standard therapy for neuroblastoma is given in 3 phases: induction, consolidation, and maintenance. For enrollment in this vaccine study patients and their physicians must anticipate therapy that will include consolidation with high dose chemotherapy with stem cell rescue. They will be eligible for enrollment in the phase I or phase II trial of vaccination with gene modified and unmodified, allogeneic neuroblastoma cell lines. Patients will receive Induction, Consolidation, and Maintenance therapy per their institutional standards. A general description of the therapy follows:
- Induction: Induction consists of multiple cycles of induction chemotherapy with harvest of autologous stem cells immediately following a particular cycle of chemotherapy per institutional standards. Local control of the tumor with radiation therapy and/or surgery occurs following a few cycles of induction chemotherapy or immediately prior to consolidation therapy.
- Consolidation: Consolidation must consist of high dose chemotherapy with autologous stem cell rescue (HDT/SCR).
- Maintenance: Starting day +90 after HDT/SCR, patients will be treated with Isotretinoin (Cis-Retinoic Acid, CRA).
VACCINE DOSING: Vaccine components SJNB-JF-IL2 and SJNB-JF-Lptn will each be dosed at 1x10e7 cells/m2. This will be given in conjunction with an escalating dose of SKNLP vaccine in the phase I portion of this study. In the phase II portion of this study, the same dose of SJNB-JF-IL2 and SJNB-JF-Lptn will be given in conjunction with the highest dose of SKNLP determined in the phase I portion. Vaccination will be administered on an inpatient or outpatient basis. Patient will be notified of which dose of vaccine cells they will receive if enrolled in the study.
Phase I Dose Escalation Component: While the investigators do not suspect that addition of a second irradiated, unmodified neuroblastoma tumor cell line to the previously tested SJNB-JF gene modified cell line will affect the safety profile of the vaccine, as the SKNLP has not been tested previously in vaccine studies, the investigators will perform an abbreviated dose escalation study of the combined vaccine to assess safety. The investigators know that the vaccine given to patients whose neuroblastoma returned was safe. The vaccine that was given to those patients was treated with the viruses to make cytokines. The investigators have never used the 2nd cell group in patients. Because of this, the investigators plan to treat 3 to 6 patients at a lower dose of cells to see if adding the second cell line is safe to give.
- Dose Level 1 (3-6 patients) 1x10e6 cells/m2/vaccination dose of SKNLP Unmodified Neuroblastoma Cell Line Vaccine Component
Dose Level 2 (3-6 patients) 1x10e7 cells/m2/vaccination dose of SKNLP Unmodified Neuroblastoma Cell Line Vaccine Component
- SJNB-JF-IL2 and SJNB-JF-Lptn cells are each dosed at 1x10e7 cells/m2/vaccination
Duration of Therapy: In the absence of treatment delays due to adverse events, treatment may continue with immunizations per the treatment plan up to 12 vaccinations or until one of the following criteria applies: - Disease progression - Intercurrent illness that prevents further administration of treatment - Unacceptable adverse events(s) including but not limited to grade 3-4 non-hematologic toxicity according to CTCAE v3.0. Grade 3 rigors/chills will be tolerated for 48-72 hours if attributed to vaccination. - Patient decides to withdraw from the study - General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgement of the investigator.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00703222
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Chrystal U Louis, MD||Baylor College of Medicine|