DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC

Kidney Cancer Clinical Trial

Official title:

A Phase II Study Of Autologous Tumor/DC Vaccine (DC Vaccine) Combined With Interleukin-2 (IL-2) And Interferon-α-2a (IFNα-2a) In Patients With Metastatic Renal Cell Carcinoma (RCC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00085436
• Other study ID #: D0238
• Secondary ID: R01CA095648P30CA
• Status: Completed
• Phase: Phase 2
• Start date: December 2003
• Est. completion date: October 2009

Study information

• Verified date: May 2018
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Vaccines made from a patient's dendritic cells and tumor cells may make the body build an immune response to kill tumor cells. Interleukin-2 may stimulate a person's lymphocytes to kill kidney cancer cells. Interferon alfa may interfere with the growth of cancer cells. Combining vaccine therapy with interleukin-2 and interferon alfa may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with interleukin-2 and interferon alfa works in treating patients with metastatic renal cell carcinoma (kidney cancer).

Description:

OBJECTIVES:

Primary

• Determine the clinical response rate in patients with metastatic renal cell carcinoma treated with autologous dendritic cells (DC) loaded with autologous tumor lysate (DC vaccine) in combination with interleukin-2 and interferon-alfa.

• Determine the toxicity of this regimen in these patients.

Secondary

• Determine, within relevant immune pathways, the treatment-related, tumor-specific immune response in patients treated with this regimen.

• Correlate tumor-specific immune response with objective clinical response in patients treated with this regimen.

OUTLINE:

• Induction therapy: Patients undergo leukapheresis on day -9. Patients receive autologous dendritic cells (DC) loaded with autologous tumor lysate (DC vaccine) by intranodal injection on days 0 and 14; interleukin-2 (IL-2) IV continuously on days 1-5 and 15-19; and interferon-alfa (IFN-α) subcutaneously (SC) once daily on days 1, 3, 5, 15, 17, and 19.

• Maintenance therapy: Patients undergo leukapheresis on days 33, 61, and 89. Patients receive DC vaccine by intranodal injection on days 42, 70, and 98; IL-2 IV continuously on days 43-47, 71-75, and 99-103; and IFN-α SC once daily on days 43, 45, 47, 71, 73, 75, 99, 101, and 103.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed metastatic renal cell carcinoma with measurable disease.

• Tumor tissue available and properly stored for lysate preparation.

• Patients must be at least 4 weeks from their last immunotherapy, radiation, surgery or chemotherapy (6 weeks for nitrosureas) and recovered from all ill effects.

• Karnofsky Performance Status =60%

• Life expectancy = twelve weeks

• Adequate end organ function:

• Hematological: ANC = 1000cells/µL, platelets = 75,000/µL, hemoglobin = 8.5 g/dl

• Liver: AST < 2 x ULN (upper limit of normal) unless due to metastases then < 5 x ULN, serum total bilirubin < 2 x ULN (except for patients with Gilbert's Syndrome)

• Renal: serum creatinine < 2.0 x ULN.

• Pulmonary: FEV1 > 2.0 liters or > 75% of predicted for height and age.

• Cardiac: No evidence of congestive heart failure, symptoms of coronary artery disease, myocardial infarction less than 6 months prior to entry, or serious cardiac arrhythmias. Patients over 40 or have had previous myocardial infarction greater than 6 months prior to entry will be required to have a negative or low probability cardiac stress test for cardiac ischemia.

• CNS: No history of brain metastases.

• Women should not be lactating and, if of childbearing age, have a negative pregnancy test within two weeks of entry to the study.

• Appropriate Contraception in both sexes

EXCLUSION CRITERIA:

• Patients may have not have been treated previously with IL-2, IFNa or autologous vaccine.

• Concomitant second malignancy except for non-melanoma skin cancer, and non- invasive cancer such as cervical CIS, superficial bladder cancer without local recurrence, breast CIS.

• In patients with a prior history of invasive malignancy, less than five years in complete remission

• Positive serology for HIV, hepatitis B or hepatitis C,

• Significant co-morbid illness such as uncontrolled diabetes or active infection that would preclude treatment on this regimen.

• Use of corticosteroids or other immunosuppression (if patient had been taking steroids, at least 4 weeks must have passed since the last dose).

• History of autoimmune disease.

Related Conditions & MeSH terms

• Kidney Cancer
• Kidney Neoplasms

Intervention

Biological:
• Aldesleukin,
Recombinant human interleukin-2 (Proleukin, Chiron Therapeutics) will be administered as a five day (120 hr) continuous intravenous infusion at a dose of 18x106 IU per square meter of body surface area per day as per the Negrier regimen (21). The treatment schedule consists of two induction cycles and three maintenance cycles. Each induction cycle consists of two five-day courses of interleukin-2 infusion separated by a nine-day break. Each maintenance cycle consists of a five-day infusion followed by 23-day rest period of no therapy.
• autologous tumor cell vaccine
we will administer 1 X 107 DC cells. The autologous tumor cell vaccine (1 X 107 cells/1cc) in lactated ringers solution and injected into one (or two if clinically necessary) inguinal lymph nodes under ultrasound guidance. Each cycle of DC vaccine will be administered alternately in the right and left inguinal lymph nodes.
• recombinant interferon alfa
Recombinant human interferon alfa-2a (Roferon, Roche), at a dose of 6 million IU per day three times a week subcutaneously will be given during the two interleukin-2 induction cycles and during each interleukin-2 maintenance cycle

Locations

Country	Name	City	State
United States	Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
Dartmouth-Hitchcock Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Schwaab T, Schwarzer A, Wolf B, Crocenzi TS, Seigne JD, Crosby NA, Cole BF, Fisher JL, Uhlenhake JC, Mellinger D, Foster C, Szczepiorkowski ZM, Webber SM, Schned AR, Harris RD, Barth RJ Jr, Heaney JA, Noelle RJ, Ernstoff MS. Clinical and immunologic effec — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Response as Measured by RECIST	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	monthly, then every 2-3 months
Secondary	Immunity as Measured by T-cell and Antibody Responses to the Tumor	All patients receiving at least one week of treatment and have at least two time points available for assessment of immune parameters will be include in the evaluation of immune status.	monthly for 5 months