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| Sponsor: | Baylor College of Medicine |
|---|---|
| Collaborator: |
Texas Children's Hospital |
| Information provided by: | Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00703222 |
Purpose
We 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.
A 3+3, phase I dose-escalation trial will be employed to assess safety of two dose levels. 3-6 patients will be enrolled at each dose level and dose-escalation rules will proceed as specified in section 5.2. A 21-day window following the first vaccination will constitute the time period for DLT assessment. Dose limiting toxicity will be any grade 3 or 4 non-hematologic toxicity as per the CTCAE v3.0 or a grade 3 injection site toxicity per the CTCAE 3.0. Exception: Grade 3 rigors/chills will be tolerated for 48-72 hours if attributable to vaccine reaction. Under the phase Iia portion, additional patients will be accrued at the MTD from the phase I portion. Prior published studies showed a 6-fold increase (range 2 - 10-fold) in vaccine specific cytotoxic T-lymphocyte precursors (CTLp) from pre to post vaccination (Institutional data; manuscript in preparation). We will use ELISPOT from blood drawn at the timepoints indicated, to assess for a change in the number of vaccine specific CTLp from baseline to 1 year after vaccination . With a cohort of 10 patients treated at the MTD, we will have 80% power to detect an alternative hypothesis of a 3.5 fold increase in CTLp (SD = 2.4) vs. a null hypothesis of 1.0 based on a two-sided, one-sample t-test with 5% alpha. We expect accrue 1 to 2 patients per month.
| Condition | Intervention | Phase |
|---|---|---|
|
Neuroblastoma |
Biological: SJNB-JF-IL2 and SJNB-JF-Lptn cells and SKNLP Unmodified Neuroblastoma Cell Lines |
Phase I Phase II |
| Study Type: | Interventional |
| Study Design: | Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study |
| 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 |
| Estimated Enrollment: | 24 |
| Study Start Date: | June 2008 |
| Estimated Study Completion Date: | July 2027 |
| Estimated Primary Completion Date: | July 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Vaccine and Dose Escalation: Experimental
Phase I Dose Escalation Component: While we 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, we will perform an abbreviated dose escalation study of the combined vaccine to assess safety. We know that the vaccine we gave to the patients whose neuroblastoma came back was safe. The vaccine that was given to those patients was treated with the viruses to make cytokines. We have never used the 2nd cell group in patients. Because of this, we 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.
|
Biological: SJNB-JF-IL2 and SJNB-JF-Lptn cells and SKNLP Unmodified Neuroblastoma Cell Lines
*SJNB-JF-IL2 and SJNB-JF-Lptn cells are each dosed at 1x10e7 cells/m2/vaccination
|
Show Detailed Description Eligibility| Ages Eligible for Study: | up to 20 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histological proof of high-risk neuroblastoma at diagnosis (see Appendices A and B in Full Protocol attached in Section S.)
Anticipating single autologous stem cell rescue following high dose consolidation chemotherapy.
Meet all eligibility criteria for high dose chemotherapy with stem cell rescue per institutional standard
Age <21 years at time of diagnosis
HIV negative
Exclusion Criteria:
Patients must not be currently receiving any investigational agents or have received any tumor vaccines within the previous six months.
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant
HIV-positive patients regardless of treatment status
Contacts and Locations| Contact: Chrystal Louis, MD | 832-822-4809 | clouis@bcm.tmc.edu |
| Contact: Malcolm Brenner, MB, PhD | 832-824-4671 | mkbrenne@txccc.org |
| United States, Texas | |
| Texas Children's Hospital | Recruiting |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: Chrystal Louis, MD | |
| Sub-Investigator: Robert A Krance, MD | |
| Sub-Investigator: Malcolm K Brenner, MD | |
| Sub-Investigator: Helen E Heslop, MD | |
| Sub-Investigator: Rachel A Egler, MD | |
| Sub-Investigator: Hao Liu | |
| Sub-Investigator: Heidi V Russell, MD | |
| Principal Investigator: | Chrystal Louis, MD | Baylor College of Medicine |
More Information
| Responsible Party: | BCM/CAGT ( Chrystal Louis ) |
| Study ID Numbers: | 22053 |
| Study First Received: | June 20, 2008 |
| Last Updated: | December 3, 2009 |
| ClinicalTrials.gov Identifier: | NCT00703222 History of Changes |
| Health Authority: | United States: Food and Drug Administration |
|
high-risk neuroblastoma single autologous stem cell rescue |
|
Neuroectodermal Tumors, Primitive Neoplasms by Histologic Type Antineoplastic Agents Physiological Effects of Drugs Neoplasms, Nerve Tissue Pharmacologic Actions Neuroblastoma Neuroectodermal Tumors Neoplasms Sensory System Agents |
Analgesics, Non-Narcotic Interleukin-2 Neoplasms, Germ Cell and Embryonal Therapeutic Uses Peripheral Nervous System Agents Analgesics Neoplasms, Neuroepithelial Central Nervous System Agents Neuroectodermal Tumors, Primitive, Peripheral Neoplasms, Glandular and Epithelial |
