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| Sponsor: | Baylor College of Medicine |
|---|---|
| Collaborators: |
Texas Children's Hospital Center for Cell and Gene Therapy, Baylor College of Medicine |
| Information provided by: | Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00085930 |
Purpose
In the beginning of this study, two different dose levels of gene modified CTL and T cells were evaluated. The investigators started at the dose given to Group 2 in the original study (1x10e8 cells/m2 ) shown in the absence of CD45 Mab to be safe but entirely ineffective (little or no detection of gene modified T cells or CTL, no persistence, no tumor response). Three to six patients were expected to be evaluated on each level. Each patient will receive one injection according to the dosing schedules.
The investigators have now analyzed expansion and persistence data for both the infused modified EBV CTL and T-cells following infusion in the 12 patients on study (3 at dose level 1; 3 at dose level 2 without lymphodepletion; and 3 at dose level 2 and 3 at dose level 3 with lymphodepletion. The investigators noted patients who received modified lymphocytes at dose level 2 and 3 did not have any higher or more prolonged persistence of their CAR-CTL than patients treated at dose level 1, and indeed there was a trend for patients treated at the lowest dose level to have the greatest "area under the curve" of percentage CAR+ cells versus time. While this observation would be counterintuitive for conventional therapeutic agents in traditional phase I dose finding trials, lymphocytes expanded ex vivo expanded lymphocytes may progressively lose their ability to expand in response to stimuli in vivo as the degree of ex vivo expansion increases to meet cell dose requirements. The investigators have certainly observed that viral specific CTL given at lower dose levels in other trials conducted by our group expand to equivalent numbers irrespective of the dose of cells given.
Our observations on this limited number of patients have prompted us to modify the protocol to discover if these observations are fortuitous or reflective of a genuine biological phenomenon. This information will be invaluable for the Phase II study which we hope to conduct given the apparent anti-tumor activity observed in 4/8 patients in the Phase I study. The investigators therefore propose to treat 6 patients at dose level 1 without lymphodepletion.
| Condition | Intervention | Phase |
|---|---|---|
|
Neuroblastoma |
Biological: 14g2a.zeta chimeric receptor transduced autologous EBV specific cytotoxic T-lymphocytes (EBV-CTL) w/o lymphodepletion |
Phase I |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Administration of Peripheral Blood T-Cells and EBV Specific CTLs Transduced to Express GD-2 Specific Chimeric T Cell Receptors to Patients With Neuroblastoma |
| Estimated Enrollment: | 18 |
| Study Start Date: | April 2003 |
| Estimated Study Completion Date: | December 2021 |
| Estimated Primary Completion Date: | December 2021 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: EBV specific CTLs without lymphodepletion |
Biological: 14g2a.zeta chimeric receptor transduced autologous EBV specific cytotoxic T-lymphocytes (EBV-CTL) w/o lymphodepletion
CTLs: 2x10e7 cells/m2
|
Show Detailed Description Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
High risk neuroblastoma with a history of persistent or relapsed disease, or after initial therapy
Patients must have a life expectancy of at least 12 weeks
Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study
Patients must not be currently receiving any investigational agents or have not received any tumor vaccines within the previous 6 weeks
Patients must have an ANC > 500, platelet count > 20,000
Patients who have received prior therapy with murine antibodies must have documentation of absence of human anti-mouse antibodies (HAMA) prior to enrollment on this study
Patients must have bilirubin less than 3 times the upper limit of normal
Patients must have AST less than 5 times the upper limit of normal
Patients must have serum creatinine less than 3 times upper limit of normal
Patient may not have cardiomegaly or bilateral pulmonary infiltrates on chest radiograph. Patients may have pulmonary metastatic lesions
Patient may not have an oxygen requirement as defined by pulse oximetry of > 90% on room air
Patients must have Karnofsky score of > 60% if > 10 years old or Lansky performance score of greater than 60% if 10 years old or younger
Patients must have autologous transduced EBV-specific CTLs and transduced peripheral blood T-cells with 15% expression or greater of 14g2a.zeta determined by flow-cytometry
Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom
Patients must not be pregnant or lactating
Patients must not have tumor in a location where enlargement could cause airway obstruction
Patients must not have a history of hypersensitivity to murine protein-containing products
Patients must not have a known sensitivity to rat monoclonal antibodies
Note: All labs must be collected within 10 days prior to initiation of study related treatment
Exclusion Criteria:
Contacts and Locations| United States, Texas | |
| Texas Children's Hospital | |
| Houston, Texas, United States, 77030 | |
| Study Chair: | Malcolm K Brenner, MD | Baylor College of Medicine |
More Information
| Responsible Party: | Chrystal Louis, MD, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00085930 History of Changes |
| Obsolete Identifiers: | NCT00609206 |
| Other Study ID Numbers: | 13149-NESTLES, NESTLES |
| Study First Received: | June 17, 2004 |
| Last Updated: | August 12, 2011 |
| Health Authority: | United States: Food and Drug Administration |
|
Neuroblastoma |
|
Neuroblastoma Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |
