Vaccination of Patients With Renal Cell Cancer With Dendritic Cell Tumor Fusions and GM-CSF

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00458536
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 38
• Location: 1
• Arms: 2
• Duration (Months): 218
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The main purpose of this study is to test the safety of the dendritic cell/tumor fusion study vaccine in combination with a laboratory-made agent called Granulocyte Macrophage Colony Stimulating Factor (GM-CSF). Another purpose is to determine the type and severity of any side effects associated with this study vaccine. GM-CSF is similar to a substance in the body that stimulates the production of white blood cells. To create the study vaccine, cells will be removed from the participants tumor and fused with dendritic cells which are obtained from the participants blood. Dendritic cells are responsible for immune responses to "foreign" substances that enter the body. Animal studies have shown that these fused cells can stimulate powerful anti-tumor responses.

Condition or Disease	Intervention/Treatment	Phase
Renal Cancer	Biological: Dendritic Cell Tumor Fusion Vaccine; Drug: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)	Phase 1/Phase 2

Detailed Description

• Patients are being asked to participate if they have chosen to undergo a "debulking nephrectomy" (surgery to remove a tumor of the kidney, but not all of the cancer cells in their body) as a standard treatment for kidney cancer or they have tumor lesions that are accessible and are being removed to treat or diagnose their cancer.

• Participants enrolled in this study will be assigned to receive a particular dose of the dendritic cell/tumor fusion vaccine cells. The dose will be determined by when they are enrolled in the study. There are two cohorts to this study. The first cohort will be given the vaccine alone. If the vaccine is well tolerated then we will proceed to the second cohort. The second cohort will receive GM-CSF in addition to the vaccine.

• Tumor cells will be collected to make the study vaccine. Based on the location of the cancer, a decision will be made as to the best approach to obtain these cells.

• Participants will undergo a procedure known as leukapheresis in order to obtain their dendritic cells. Prior to this procedure they will receive 1 to 2 injection of GM-CSF to help increase their white blood cell count.

• If sufficient numbers of cells are obtained, tumor cells and dendritic cells will be fused (mixed) together in the laboratory and divided into the appropriate doses for administration.

• The treatment will consist of 3 vaccinations of fused cells given by an injection under your skin at 3-week intervals. The first six participants will receive only the study vaccine. The remaining participants will receive the study vaccine combined with GM-CSF.

• If enough vaccine cannot be made for the participant to receive 3 doses, the participant may receive only 2 doses of the study vaccine.

• Approximately 3 to 4 tablespoons of blood will be collected at certain times for testing the immune system and to determine if the study vaccine has increased the immune response against the tumor cells. Weekly visits for physical exam, assessment of adverse events and safety labs will be conducted.

• Regular blood draws will be done for at least 6 months following the completion of the study to follow safety labs and to monitor the immune response. Monthly physical exams will be performed following the last injection of the study vaccine. At one month, three months, and six months following the date the participant received the last study vaccine, they will have a CT scan to see if the study vaccine has affected their disease.

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Vaccination of Patients With Renal Cell Cancer With Dendritic Cell Tumor Fusions and GM-CSF
• Study Start Date: Oct 1, 2004
• Actual Primary Completion Date: Dec 1, 2014
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Patients treated with DC/RCC vaccine to evaluate for treatment-limiting toxicity	Biological: Dendritic Cell Tumor Fusion Vaccine; 3 vaccinations at three week intervals; Drug: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF); Combined with the vaccine in the remaining subjects after the first 6 are enrolled.
Experimental: Cohort 2 Patients treated with DC/RCC vaccine to evaluate response	Biological: Dendritic Cell Tumor Fusion Vaccine; 3 vaccinations at three week intervals; Drug: Granulocyte Macrophage Colony Stimulating Factor (GM-CSF); Combined with the vaccine in the remaining subjects after the first 6 are enrolled.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events Associated With Vaccination With Mature DC/Tumor Fusion and GM-CSF [5 years]

Secondary Outcome Measures

1. To Determine if Cellular and Humoral Immunity is Induced by Serial Vaccination With DC/Tumor Fusion Cells and GM-CSF [5 years]

2. to Correlate Immunologic Response Following Vaccination. [5 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with stage IV renal cancer who have not received prior chemotherapy or biological therapy

• Patients who are to undergo debulking nephrectomy for independent clinical indications or patients with other sites of accessible disease

• Tumor tissue should be at least 2.0cm in longest dimension

• Patients should meet prognostic criteria for intermediate or favorable risk disease as defined by Motzer criteria

• Measurable metastatic disease as defined by a lesion of at least 1cm outside the lesion used for vaccine generation and exclusive of bony metastases

• ECOG Performance Status of 0-2 with greater than six week life expectancy

• 18 years of age or older

• Lab results within range outlined in protocol

Exclusion Criteria:

• Patients who have received prior chemotherapy

• Clinical evidence of CNS disease. Patients with a history of treated brain metastasis must be stable with no evidence of disease for 3 months

• HIV positive

• Serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, unstable ischemic coronary disease or congestive heart failure

• Pregnant of lactating women

• History of clinically significant venous thromboembolism

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Avigan, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: David Avigan, MD, Principal Investigator, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT00458536
• Other Study ID Numbers: 04-117
• First Posted: Apr 11, 2007
• Last Update Posted: Feb 1, 2022
• Last Verified: Jan 1, 2022

• Keywords provided by David Avigan, MD, Principal Investigator, Beth Israel Deaconess Medical Center: GM-CSF; vaccine; debulking nephrectomy; dendritic cells
• Additional relevant MeSH terms: Carcinoma, Renal Cell; Kidney Neoplasms; Molgramostim; Sargramostim

Study Results

Participant Flow

Arm/Group Title	Patients Treated With Vaccine
Arm/Group Description	Patients with renal cell carcinoma following debulking nephrectomy who receive at least 2 doses of DC/renal fusion vaccine.
Period Title: Overall Study
STARTED	38
COMPLETED	19
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Patients Treated With Vaccine
Arm/Group Description	Patients with renal cell carcinoma following debulking nephrectomy who receive at least 2 doses of DC/renal fusion vaccine.
Overall Participants	19
Age, Customized (years) [Median (Full Range) ]
Median (Full Range) [years]	56
Sex: Female, Male (Count of Participants)
Female	6 31.6%
Male	13 68.4%
Region of Enrollment (participants) [Number]
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events Associated With Vaccination With Mature DC/Tumor Fusion and GM-CSF
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

Adverse events potentially related to vaccination were largely restricted to injection site reactions. 12 of the 19 patients experienced vaccine site reactions.

Arm/Group Title	Patients Treated With Vaccine
Arm/Group Description	Patients with renal cell carcinoma following debulking nephrectomy who receive at least 2 doses of DC/renal fusion vaccine.
Measure Participants	19
Number [participants]	12 63.2%

2. Secondary Outcome

Title	To Determine if Cellular and Humoral Immunity is Induced by Serial Vaccination With DC/Tumor Fusion Cells and GM-CSF
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	to Correlate Immunologic Response Following Vaccination.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	AEs were collected over the course of the study while patients were being treated. This spanned 4 years.
Arm/Group Title	Patients Treated With Vaccine
Arm/Group Description	Patients with renal cell carcinoma following debulking nephrectomy who receive at least 2 doses of DC/renal fusion vaccine.
All Cause Mortality
	Patients Treated With Vaccine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Patients Treated With Vaccine
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Other (Not Including Serious) Adverse Events
	Patients Treated With Vaccine
	Affected / at Risk (%)	# Events
Total	16/19 (84.2%)
Blood and lymphatic system disorders
Bruising (at site of vaccine)	3/19 (15.8%)	7
Investigations
Injection Site Reaction	12/19 (63.2%)	25
Urticaria	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Arthralgias	1/19 (5.3%)	2

Limitations/Caveats

[Not Specified]

More Information

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.