Anti-gp100 Cells Plus ALVAC gp100 Vaccine to Treat Advanced Melanoma - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Metastatic Melanoma Skin Cancer
Interventions:	Drug: cyclophosphamide Drug: fludarabine phosphate Biological: Aldesleukin Biological: ALVAC gp100 Vaccine Biological: anti-gp100:154-162 Tcell receptor (TCR) peripheral blood lymphocyte (PBL)

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Three participants was enrolled in this study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
ALVAC Plus Anti-gp100:154-162 TCR PBL + HD IL-2	ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + HD interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 CCID50 (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14. 3 x 10^11 anti-gp100:154-162 TCR engineered PBL by intravenous infusion. A minimum of approximately 5 x 10^8 cells will be given. Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)– 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)

Description

ALVAC Plus Anti-gp100:154-162 TCR PBL + HD IL-2

ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + HD interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 CCID50 (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.

3 x 10^11 anti-gp100:154-162 TCR engineered PBL by intravenous infusion. A minimum of approximately 5 x 10^8 cells will be given.

Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)– 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)

Participant Flow: Overall Study

	ALVAC Plus Anti-gp100:154-162 TCR PBL + HD IL-2
STARTED	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

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Reporting Groups

	Description
ALVAC Plus Anti-gp100:154-162 TCR PBL + HD IL-2	ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + HD interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 CCID50 (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14. 3 x 10^11 anti-gp100:154-162 TCR engineered PBL by intravenous infusion. A minimum of approximately 5 x 10^8 cells will be given. Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)– 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)

Description

ALVAC Plus Anti-gp100:154-162 TCR PBL + HD IL-2

ALVAC plus anti-gp100:154-162 T cell receptor (TCR) peripheral blood lymphocytes (PBL) + HD interleukin-2 (IL-2): ALVAC vaccine two hours prior to cell infusion patients will receive 0.5 ml containing a target dose of 10^7 CCID50 (with a range of approximately 10^6.4 to 107.9/mL of the gp100 ALVAC virus subcutaneously in each extremity (total of 4 x 10^7 CCID50/2mL. This will be repeated on day 14.

3 x 10^11 anti-gp100:154-162 TCR engineered PBL by intravenous infusion. A minimum of approximately 5 x 10^8 cells will be given.

Aldesleukin (IL2, Proleukin, Recombinant human interleukin 2)– 720,000 IU/kg intravenous over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses)

Baseline Measures

	ALVAC Plus Anti-gp100:154-162 TCR PBL + HD IL-2
Number of Participants [units: participants]	3
Age [units: participants]
<=18 years	0
Between 18 and 65 years	3
>=65 years	0
Age [units: years] Mean ± Standard Deviation	33.3 ± 6.0
Gender [units: participants]
Female	2
Male	1
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	0
Not Hispanic or Latino	3
Unknown or Not Reported	0
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	0
White	3
More than one race	0
Unknown or Not Reported	0
Region of Enrollment [units: participants]
United States	3

Outcome Measures

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1. Primary:

Number of Participants With Metastatic Melanoma Who Develop Clinical Tumor Regression (CR or PR) [ Time Frame: 4-6 weeks after treatment and then monthly for approximately 3 to 4 months or until off study criteria are met ]

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2. Secondary:

Number of Participants With in Vivo Survival of T-cell Receptor (TCR) Gene-engineered Cells. [ Time Frame: 1 month ]

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3. Secondary:

Number of Participants With Adverse Events [ Time Frame: 18.5 months ]

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4. Secondary:

Number of Participants Who Develop Anti-mouse T Cell Receptor (TCR) Antibodies [ Time Frame: 1 month ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Early termination leading to a small number of subjects analyzed.

Results Point of Contact:

Name/Title: Steven A. Rosenberg, M.D.
Organization: National Cancer Institute, National Institues of Health
phone: 301-496-4164
e-mail: sar@mail.nih.gov

Publications:

Kawakami Y, Eliyahu S, Delgado CH, Robbins PF, Rivoltini L, Topalian SL, Miki T, Rosenberg SA. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3515-9.

Kawakami Y, Eliyahu S, Sakaguchi K, Robbins PF, Rivoltini L, Yannelli JR, Appella E, Rosenberg SA. Identification of the immunodominant peptides of the MART-1 human melanoma antigen recognized by the majority of HLA-A2-restricted tumor infiltrating lymphocytes. J Exp Med. 1994 Jul 1;180(1):347-52.

Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995 Oct 19;333(16):1038-44.

Responsible Party:	Steven A. Rosenberg, M.D./National Cancer Institute, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00610311 History of Changes
Other Study ID Numbers:	080055, 08-C-0055
Study First Received:	February 6, 2008
Results First Received:	March 14, 2012
Last Updated:	October 18, 2012
Health Authority:	United States: Federal Government United States: Food and Drug Administration