Gene-Modified Lymphocytes, High-Dose Aldesleukin, and Vaccine Therapy in Treating Patients With Progressive or Recurrent Metastatic Cancer

Phase 2

Terminated

• Conditions: Melanoma (Skin); Kidney Cancer; Unspecified Adult Solid Tumor, Protocol Specific
• Interventions: Biological: aldesleukin; Biological: anti-p53 T-cell receptor-transduced peripheral blood lymphocytes; Biological: autologous dendritic cell-adenovirus p53 vaccine; Biological: filgrastim; Drug: cyclophosphamide; Drug: fludarabine phosphate

• Registration Number: NCT00704938
• Lead Sponsor: National Institutes of Health Clinical Center (CC)

Brief Summary

RATIONALE: Gene-modified lymphocytes may stimulate the immune system in different ways and stop tumor cells from growing. High-dose aldesleukin may stimulate lymphocytes to kill tumor cells. Vaccines made from a gene modified virus and a person's dendritic cells may help the body build an effective immune response to kill tumor cells. Giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gene-modified lymphocytes together with high-dose aldesleukin and vaccine therapy works in treating patients with progressive or recurrent metastatic cancer.

Detailed Description

OBJECTIVES:

Primary

* Determine if the administration of anti-p53 T-cell receptor (TCR) gene-engineered peripheral blood lymphocytes, high-dose aldesleukin, and adenovirus p53 dendritic cell (DC) vaccine after a nonmyeloablative, but lymphoid-depleting, preparative regimen will result in clinical tumor regression in patients with metastatic cancer that overexpresses p53.

Secondary

* Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.

* Determine the ability of a dendritic cell (DC) vaccine to restimulate TCR gene-engineered cells in vivo.

* Determine the toxicity profile of this treatment regimen.

OUTLINE: Patients are stratified according to type of metastatic cancer (melanoma or renal cell cancer vs all other cancers).

* Peripheral blood mononuclear cell (PBMC) collection: Patients undergo PBMC collection via leukapheresis for the generation of the adenovirus p53 dendritic cell vaccine as well as anti-p53 T-cell receptor (TCR) gene-engineered peripheral blood lymphocytes.

* Nonmyeloablative lymphocyte-depleting preparative regimen: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.

* Peripheral blood lymphocyte infusion: Patients receive anti-p53 TCR gene-engineered peripheral blood lymphocytes IV over 20-30 minutes on day 0. Patients receive filgrastim (growth colony stimulating factor (G-CSF)) subcutaneously (SC) once daily beginning on day 1 or 2 and continuing until blood counts recover.

* High-dose aldesleukin: Patients receive high-dose aldesleukin IV over 15 minutes three times daily on days 0-4 for up to 15 doses.

* Dendritic cell vaccine: Patients receive adenovirus p53 dendritic cell vaccine SC on days 0, 7, 14, and 28.

Patients may receive one re-treatment course as above (nonmyeloablative preparative regimen, peripheral blood lymphocyte infusion, high-dose aldesleukin, and dendritic cell vaccinations) beginning 6-8 weeks after the last dose of high-dose aldesleukin.

After completion of study treatment, patients are followed periodically for up to 15 years.

Study Timeline

• Study Start: 2008-06
• Study First Submitted: 2008-06-24
• Study First Submitted QC: 2008-06-24
• Study First Posted: 2008-06-25
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Results First Submitted: 2012-07-10
• Results First Submitted QC: 2012-07-10
• Results First Posted: 2012-08-14
• Status Verified: 2015-09
• Last Update Submitted: 2015-10-06
• Last Update Posted: 2015-10-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC	anti-p53 T-cell receptor-transduced peripheral blood lymphocytes	Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC	filgrastim	Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Other histology	anti-p53 T-cell receptor-transduced peripheral blood lymphocytes	Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC	aldesleukin	Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC	cyclophosphamide	Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Other histology	filgrastim	Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Other histology	fludarabine phosphate	Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC	autologous dendritic cell-adenovirus p53 vaccine	Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Other histology	aldesleukin	Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Other histology	autologous dendritic cell-adenovirus p53 vaccine	Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Melanoma/RCC	fludarabine phosphate	Patients with melanoma and renal cell cancer will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)
anti-p53 TCR PBL + DC + IL-2: Other histology	cyclophosphamide	Patients with other histologies, such as breast cancer, will receive anti-p53 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + dendritic cells (DC) + interleukin-2 (IL-2)

Primary Outcome Measures

Name	Time	Method
Clinical Response (Complete Response + Partial Response)	5 months	Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all lesions. Partial response is a 30% decrease in the sum of the longest diameter (LD) of target lesions.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	5 months	Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse events module.

Trial Locations

Locations (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office; 🇺🇸 Bethesda, Maryland, United States