Pilot Study of Denileukin Diftitox Plus High-Dose IL-2 for Patients With Metastatic Renal Cancer

NCT ID: NCT00278369

Last Updated: 2013-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2010-09-30

Brief Summary

RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry tumor-killing substances directly to kidney cancer cells. Interleukin-2 may stimulate the white blood cells to kill kidney cancer cells. Giving denileukin diftitox together with interleukin-2 may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects of denileukin diftitox and interleukin-2 in treating patients with metastatic kidney cancer.

Detailed Description

OBJECTIVES:

Primary

• Determine the toxic effects of denileukin diftitox and high-dose interleukin-2 in patients with metastatic renal cell cancer.

Secondary

• Perform transforming growth factor (TGF)-beta promoter and TGF-beta receptor genotyping to search for variants that may be associated with tumor response to therapy.
• Determine the overall response rate (partial and complete) in patients treated with this regimen.
• Determine the time to progression in patients treated with this regimen.

OUTLINE: This is a randomized, pilot study.

The first 3 patients enrolled in the study receive high-dose interleukin-2 (IL-2) IV over 15 minutes, 3 times daily, on days 1-5 and 15-19 and denileukin diftitox IV over 15-60 minutes once daily on days 8-10. If no dose-limiting toxicity occurs after receiving denileukin diftitox, subsequent patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes once daily on days -4 to -2 and high-dose IL-2 IV over 15 minutes, 3 times daily, on days 1-5 and 15-19.
• Arm II: Patients receive high-dose IL-2 as in arm I and denileukin diftitox (at a higher dose than for the first 3 patients enrolled in the study) IV over 15-60 minutes at a higher dose once daily on days 8-10.

All patients may receive additional treatment with IL-2 alone in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 4 years.

PROJECTED ACCRUAL: A total of 13 patients will be accrued for this study.

Conditions

Kidney Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

6 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course

Group Type: EXPERIMENTAL

aldesleukin

Intervention Type: BIOLOGICAL

The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment

denileukin diftitox

Intervention Type: BIOLOGICAL

Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.

B

9 mcg/kg Denileukin Diftitox administered IV/daily on days -4 to -2 of standard interleukin 2 dose course

Group Type: EXPERIMENTAL

aldesleukin

Intervention Type: BIOLOGICAL

The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment

denileukin diftitox

Intervention Type: BIOLOGICAL

Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.

C

9 mcg/kg Denileukin Diftitox administered IV/daily on days 8-10 of standard interleukin 2 dose course

Group Type: EXPERIMENTAL

aldesleukin

Intervention Type: BIOLOGICAL

The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment

denileukin diftitox

Intervention Type: BIOLOGICAL

Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.

Interventions

aldesleukin

The IL-2 is given as a 15-minute infusion through an intravenous catheter (I.V.), a small plastic tube that is put into your vein for the time you are receiving the study treatment. IL-2 is given through the I.V. once every 8 hours for 5 days (days 1-5). A second 5 day cycle of IL-2 will begin on the 15th day (days 15-19). This is one complete cycle (days 1-19) of IL-2 treatment

Intervention Type: BIOLOGICAL

denileukin diftitox

Denileukin diftitox will be administered once daily as a 15 to 60 minute infusion for 3 consecutive days.

Intervention Type: BIOLOGICAL

Other Intervention Names

IL-2; Interleukin-2; Proleukin; ONTAK (denileukin diftitox); DAB 389 IL-2

Eligibility Criteria

Exclusion Criteria

• Adequate pulmonary reserve

• Pulmonary function tests (PFTs) must be performed within 42 days of IL-2 treatment

• FEV_1 > 2.0 liters of > 75% predicted for height and age
• Patients unable to perform PFTs will be excluded
• Women who are pregnant or lactating are not eligible
• Women of childbearing potential and sexually active males must commit to the use of effective contraception while on study
• Negative pregnancy test
• No known HIV-positive patients
• No evidence of active infection requiring antibiotic therapy
• Must not have a contraindication to treatment with pressor agents
• Must not have any significant medical disease that, in the opinion of the investigator, may interfere with completion of the study
• No history of another malignancy within the past 5 years other than basal cell skin cancer

PRIOR CONCURRENT THERAPY:

• Recovered from all toxic effects of prior therapy
• Must not currently receive chronic medication for asthma
• No prior interleukin-2 (IL-2) therapy
• No prior organ allografts
• No systemic corticosteroids in the 4 weeks prior to treatment
• No concurrent systemic steroids
• No radiotherapy, chemotherapy, or immunotherapy in the 4 weeks prior to the first dose of study treatment
• No concurrent radiotherapy, chemotherapy, or other immunotherapy
• No previous investigational agent within 4 weeks prior to the start of study treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Timothy Kuzel

Timothy Kuzel, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Timothy M. Kuzel, MD

Role: STUDY_CHAIR

Robert H. Lurie Cancer Center

Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

P30CA060553

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NU-04U1

Identifier Type: -

Identifier Source: secondary_id

STU00006770

Identifier Type: OTHER

Identifier Source: secondary_id

NU 04U1

Identifier Type: -

Identifier Source: org_study_id