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2025-12-24 @ 9:11 PM
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2025-12-29 @ 6:17 AM
Study NCT ID:
NCT00091104
Status:
COMPLETED
Last Update Posted:
2012-03-15
First Post:
2004-09-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cyclophosphamide and Fludarabine Followed by Vaccine Therapy, Gene-Modified White Blood Cell Infusions, and Aldesleukin in Treating Patients With Metastatic Melanoma
Sponsor:
National Institutes of Health Clinical Center (CC)
Organization:
Study Overview
Official Title:
A Study in Metastatic Melanoma Using a Lymphodepleting Conditioning Followed by Infusion of Anti-MART-1 TCR-Gene Engineered Lymphocytes and Subsequent Peptide Immunization
Status:
COMPLETED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine before a white blood cell infusion may suppress the immune system and allow tumor cells to be killed. Vaccines may make the body build an immune response to kill tumor cells. Aldesleukin may stimulate a person's white blood cells to kill tumor cells. Combining white blood cell infusion with vaccine therapy and aldesleukin may cause a stronger immune response and kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.
PURPOSE: This phase I trial is studying the side effects and best dose of gene-modified white blood cells when given together with cyclophosphamide, fludarabine, vaccine therapy, and aldesleukin and to see how well it works in treating patients with metastatic melanoma.
Detailed Description:
OBJECTIVES:
Primary
* Determine the safety of peripheral blood lymphocytes (PBLs) retrovirally transduced with an anti-MART-1 T-cell receptor (TCR) gene followed by high-dose aldesleukin (IL-2) and MART-1:27-35 peptide vaccine in patients with HLA-A\*0201-positive metastatic melanoma receiving a myeloablative preparative regimen comprising cyclophosphamide, fludarabine phosphate, and total-body irradiation.
* Determine, preliminarily, whether antitumor antigen TCR-engineered tumor-infiltrating lymphocytes or PBLs followed by IL-2 and MART-1:26-35 after a nonmyeloablative but lymphoid-depleting preparative regimen will result in clinical tumor regression in these patients.
Secondary
* Determine the in vivo survival of TCR gene-engineered cells from these patients.
* Evaluate, preliminarily, clinical response in these patients.
OUTLINE: Patients with resectable tumor undergo tumor biopsy. Tumor-infiltrating lymphocytes (TILs) from the tumor sample are cultured in vitro and tested for reactivity to melanoma antigens. Patients who are unable to undergo biopsy or whose TILs do not grow in culture are assigned to groups I or II. Patients whose tumors yield TILs that do not exhibit melanoma reactivity are assigned to group III. Patients with TILs that exhibit melanoma reactivity are removed from the study.
* Autologous stem cell collection: Patients undergo stem cell collection on treatment protocol NCI-03-C-0277 for reinfusion after the myeloablation and cell therapy. Patients receive filgrastim (G-CSF) subcutaneously (SC) twice daily beginning on day 0 and continuing for up to 5 days. Patients then undergo stem cell collection by apheresis or bone marrow harvest beginning on day 5 and continuing for up to 3 days. Some patients may receive a second course of G-CSF and undergo additional stem cell collection by apheresis or undergo treatment as outlined in group II.
* Group I (peripheral blood lymphocytes \[PBLs\] with myeloablative preparative regimen): Patients receive a myeloablative preparative regimen comprising cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine phosphate IV over 15-30 minutes on days -7 to -3, and total-body irradiation twice daily on days -3 to -1. Patients also receive autologous in vitro tumor-reactive, T-cell receptor (TCR) gene-transduced PBLs IV over 20-30 minutes on day 1 and aldesleukin IV over 15 minutes every 8 hours on days 1-5, and G-CSF SC daily beginning on day 1 and continuing until blood counts recover.
* Group II (PBLs with nonmyeloablative preparative regimen): Patients who do not meet the eligibility criteria for group I receive a nonmyeloablative preparative regimen comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1. Patients then receive aldesleukin, and G-CSF as in group I.
* Group III (autologous transduced TILs): Patients who have resected tumors that yield viable TILs have their TILs transduced with the anti-MART-1 TCR gene retroviral vector. Patients receive cyclophosphamide and fludarabine phosphate as in group II. Patients then receive autologous transduced TILs IV over 20-30 minutes on day 0. Patients also receive G-CSF and high-dose aldesleukin as in group I.
All patients receive peptide immunizations with MART-1:27-35 peptide vaccine emulsified in incomplete Freund's adjuvant SC on days 0-4, 11, 18, and 25.
In groups II or III, treatment may repeat once 6-8 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Treatment may consist of the first type cell infusion or patients may crossover to receive the other cell infusion (PBLs vs TILs).
After completion of study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: A total of 136 patients will be accrued for this study.
Primary
* Determine the safety of peripheral blood lymphocytes (PBLs) retrovirally transduced with an anti-MART-1 T-cell receptor (TCR) gene followed by high-dose aldesleukin (IL-2) and MART-1:27-35 peptide vaccine in patients with HLA-A\*0201-positive metastatic melanoma receiving a myeloablative preparative regimen comprising cyclophosphamide, fludarabine phosphate, and total-body irradiation.
* Determine, preliminarily, whether antitumor antigen TCR-engineered tumor-infiltrating lymphocytes or PBLs followed by IL-2 and MART-1:26-35 after a nonmyeloablative but lymphoid-depleting preparative regimen will result in clinical tumor regression in these patients.
Secondary
* Determine the in vivo survival of TCR gene-engineered cells from these patients.
* Evaluate, preliminarily, clinical response in these patients.
OUTLINE: Patients with resectable tumor undergo tumor biopsy. Tumor-infiltrating lymphocytes (TILs) from the tumor sample are cultured in vitro and tested for reactivity to melanoma antigens. Patients who are unable to undergo biopsy or whose TILs do not grow in culture are assigned to groups I or II. Patients whose tumors yield TILs that do not exhibit melanoma reactivity are assigned to group III. Patients with TILs that exhibit melanoma reactivity are removed from the study.
* Autologous stem cell collection: Patients undergo stem cell collection on treatment protocol NCI-03-C-0277 for reinfusion after the myeloablation and cell therapy. Patients receive filgrastim (G-CSF) subcutaneously (SC) twice daily beginning on day 0 and continuing for up to 5 days. Patients then undergo stem cell collection by apheresis or bone marrow harvest beginning on day 5 and continuing for up to 3 days. Some patients may receive a second course of G-CSF and undergo additional stem cell collection by apheresis or undergo treatment as outlined in group II.
* Group I (peripheral blood lymphocytes \[PBLs\] with myeloablative preparative regimen): Patients receive a myeloablative preparative regimen comprising cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine phosphate IV over 15-30 minutes on days -7 to -3, and total-body irradiation twice daily on days -3 to -1. Patients also receive autologous in vitro tumor-reactive, T-cell receptor (TCR) gene-transduced PBLs IV over 20-30 minutes on day 1 and aldesleukin IV over 15 minutes every 8 hours on days 1-5, and G-CSF SC daily beginning on day 1 and continuing until blood counts recover.
* Group II (PBLs with nonmyeloablative preparative regimen): Patients who do not meet the eligibility criteria for group I receive a nonmyeloablative preparative regimen comprising cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1. Patients then receive aldesleukin, and G-CSF as in group I.
* Group III (autologous transduced TILs): Patients who have resected tumors that yield viable TILs have their TILs transduced with the anti-MART-1 TCR gene retroviral vector. Patients receive cyclophosphamide and fludarabine phosphate as in group II. Patients then receive autologous transduced TILs IV over 20-30 minutes on day 0. Patients also receive G-CSF and high-dose aldesleukin as in group I.
All patients receive peptide immunizations with MART-1:27-35 peptide vaccine emulsified in incomplete Freund's adjuvant SC on days 0-4, 11, 18, and 25.
In groups II or III, treatment may repeat once 6-8 weeks later for a total of 2 courses in the absence of disease progression or unacceptable toxicity. Treatment may consist of the first type cell infusion or patients may crossover to receive the other cell infusion (PBLs vs TILs).
After completion of study treatment, patients are followed periodically for at least 5 years.
PROJECTED ACCRUAL: A total of 136 patients will be accrued for this study.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: