Clinical trial NCT00085436: DC Vaccine Combined With IL-2 and IFNα-2a in Treating Patients With mRCC
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Cancer
Keywords: recurrent renal cell cancer
stage IV renal cell cancer
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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, IFNα 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.

Primary outcomes:
measure: Clinical Response as Measured by RECIST
timeFrame: monthly, then every 2-3 months
Secondary outcomes:
measure: Immunity as Measured by T-cell and Antibody Responses to the Tumor
timeFrame: monthly for 5 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth - Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Norris Cotton Cancer Center
name: Marc S. Ernstoff, MD
role: STUDY_CHAIR
References:
citation: 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 effects of intranodal autologous tumor lysate-dendritic cell vaccine with Aldesleukin (Interleukin 2) and IFN-alpha2a therapy in metastatic renal cell carcinoma patients. Clin Cancer Res. 2009 Aug 1;15(15):4986-92. doi: 10.1158/1078-0432.CCR-08-3240. Epub 2009 Jul 21.