Adoptive Immunotherapy, Aldesleukin, and Zoledronate in Treating Patients With Stage IV Kidney Cancer and Lung Metastases

Phase I/II Study of Adoptive Immunotherapy Comprising Pyrophosphomonoester Antigen-stimulated T Cells, IL-2, and Nitrogen-containing Bisphosphonates in Patients With Stage IV Renal Cell Carcinoma

RATIONALE: Cellular adoptive immunotherapy uses a person's white blood cells that are treated in the laboratory to stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may help the laboratory-treated white blood cells stay in the body longer. Drugs used in chemotherapy, such as zoledronic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cellular adoptive immunotherapy together with interleukin-2 and zoledronic acid may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of giving cellular adoptive immunotherapy together with aldesleukin and zoledronic acid and to see how well it works in treating patients with stage IV kidney cancer and lung metastases.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer; Metastatic Cancer
• Intervention / Treatment: Biological: aldesleukin; Drug: zoledronic acid; Biological: therapeutic autologous lymphocytes

Detailed Description

OBJECTIVES:

• Determine the safety of adoptive immunotherapy comprising 2-methyl-3-butenyl-1-pyrophosphate-stimulated gamma delta (gd) T cells, zoledronate, and IL-2 after nephrectomy, especially with regard to the incidence and frequency of adverse events.
• Determine the duration of in vivo persistence of the transferred gd T cells in patients.
• Determine the doubling time of tumor growth before and after adoptive immunotherapy.
• Determine the tumor-size reducing effect of adoptive immunotherapy based on the Best Overall Response Chart.

OUTLINE: Patients undergo leukapheresis for the harvest of peripheral blood mononuclear cells (PBMCs). PBMCs are stimulated with 2-methyl-3-butenyl-1-pyrophosphate and aldesleukin for 11 days. Patients then receive the expanded Gamma Delta T cells, aldesleukin, and zoledronic acid once a month for 6 months.

After completion of study treatment, patients are followed for up to 1 month.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Kyoto University hospital
  • Tokyo, Japan, 162-8666
    • Tokyo Women's Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed renal carcinoma

  • Stage IV disease with lung metastases
• Bidimensionally measurable lung metastases by CT scan

• Meets 1 or more of the following criteria:

  • No change in disease status or progressive disease after prior aldesleukin administration for 3 months or more
  • Lung metastases after treatment with prior nephrectomy

• Patients with clear cell renal carcinoma must have undergone nephrectomy prior to study entry

  • Patients with progression of metastatic lung cancer after nephrectomy also must have received interferon alfa for 3 months or more (prior to study entry)

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Life expectancy > 6 months
• Leukocyte count ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Serum bilirubin ≤ 1.5 mg/dL
• AST/ALT ≤ 2.5 times normal
• Serum creatinine ≤ 1.7 mg/dL
• LDH ≤ 1.5 times normal
• Not pregnant nor nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection with hepatitis virus or HIV
• No poorly controlled heart failure or arrhythmia
• No hypercalcemia that require medication
• No C-reactive protein with an infectious disease that requires medication

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 3 weeks since prior chemotherapy, radiation therapy, or biologic therapy
• No prior bone marrow transplantation or organ transplantation
• No concurrent steroid therapy
• No concurrent antidepressant therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Frequency and severity of adverse events based on NCI-CTCAE version 3.0
Proportion of gd T-cells in peripheral blood

Secondary Outcome Measures

Outcome Measure
Overall response
Secondary doubling time of tumor growth

Collaborators and Investigators

• Sponsor: Tokyo Women's Medical University
• Investigators: Study Chair: Hirohito Kobayashi, Tokyo Women's Medical University

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 28, 2007
• First Posted (Estimate): January 9, 2008

Study Record Updates

• Last Update Posted (Estimate): July 10, 2013
• Last Update Submitted That Met QC Criteria: July 9, 2013
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; clear cell renal cell carcinoma; lung metastases
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Bone Density Conservation Agents; Aldesleukin; Zoledronic Acid
• Other Study ID Numbers: TRIC-CTR-GU-05-01; CDR0000581156 (Registry Identifier: PDQ (Physician Data Query))