NCT01021059

A Phase I Study of Intravenous Recombinant Human IL-15 in Adults With Refractory Metastatic Malignant Melanoma and Metastatic Renal Cell Cancer

Completed Phase 1 Last updated 8 November 2019

What this trial tests

Phase 1 trial testing rh IL-15 in Melanoma in 18 participants. Completed in 25 October 2016.

Timeline

10 November 2009

Primary endpoint
31 May 2013

25 October 2016

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	18
Start date	10 November 2009
Primary completion	31 May 2013
Estimated completion	25 October 2016
Sites	1 location across United States

Drugs / interventions tested

• rh IL-15 — full drug profile →

Conditions studied

• Melanoma — all drugs for Melanoma →
• Carcinoma, Renal Cell — all drugs for Carcinoma, Renal Cell →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 85, any sex, with Melanoma or Carcinoma, Renal Cell. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Background:

* Recombinant human interleukin-15 (rhIL-15) is a substance that is naturally produced in the body that has many properties that increase the activity and strength of the immune system, the body s natural defense system. It is hoped that rhIL-15 can boost or strengthen patients immune systems and restore immune responses against cancer and infectious diseases like HIV.
* rhIL-15 is being studied in patients with malignant melanoma, an aggressive type of skin cancer, and in patients with renal cell carcinoma, a type of kidney cancer that has spread to other parts of the body. Researchers are interested in determining if rhIL-15 can help stimulate the immune system and aid in the treatment process for cancers that have not responded well to standard therapies.

Objectives:

* To determine whether rhIL-15 is safe and effective in the treatment of metastatic malignant melanoma or metastatic renal cell carcinoma
* To examine how the body processes rhIL-15 after each infusion and determine how it acts on the treated cancer.

Eligibility:

* Patients older than 18 years of age that have been diagnosed with metastatic malignant melanoma or metastatic renal cell carcinoma that has not responded to standard treatments.
* Eligible patients may not have received prior treatment with interleukin-2.

Design:

* Prior to treatment, patients will have baseline blood tests and imaging scans.
* Participants will be admitted to an in-patient unit of the NIH Clinical Center for this treatment. rhIL-15 will be given intravenously once a day for 12 consecutive days, for a total of twelve doses of the drug. The injection of rhIL-15 will take about 30 minutes. Patients will be evaluated daily before each treatment and more frequently if necessary.
* During the 12-day treatment and for at least 42 days from the start of the treatment, patients will be closely followed for possible side effects and for tumor response. Blood will be drawn frequently for monitoring purposes, and other procedures such as chest x-rays and imaging scans will be performed to monitor the state of the tumor and the patient response to treatment.
* After completing the rhIL-15 treatment and discharge from the hospital, patients will have an evaluation with a member of the research team once a week from the end of the treatment period to 42 days from the start of the treatment.
* Study doctors may ask patients to return for evaluation (including blood draws) at 3 and 6 months after the completion of the treatment, checking for potential long-term effects or toxicity of the treatment.

Background:

* Recombinant human interleukin-15 (rhIL-15) is a substance that is naturally produced in the body that has many properties that increase the activity and strength of the immune system, the body s natural defense system. It is hoped that rhIL-15 can boost or strengthen patients immune systems and restore immune responses against cancer and infectious diseases like HIV.
* rhIL-15 is being studied in patients with malignant melanoma, an aggressive type of skin cancer, and in patients with renal cell carcinoma, a type of kidney cancer that has spread to other parts of the body. Researchers are interested in determining if rhIL-15 can help stimulate the immune system and aid in the treatment process for cancers that have not responded well to standard therapies.

Objectives:

* To determine whether rhIL-15 is safe and effective in the treatment of metastatic malignant melanoma or metastatic renal cell carcinoma
* To examine how the body processes rhIL-15 after each infusion and determine how it acts on the treated cancer.

Eligibility:

* Patients older than 18 years of age that have been diagnosed with metastatic malignant melanoma or metastatic renal cell carcinoma that has not responded to standard treatments.
* Eligible patients may not have received prior treatment with interleukin-2.

Design:

* Prior to treatment, patients will have baseline blood tests and imaging scans.
* Participants will be admitted to an in-patient unit of the NIH Clinical Center for this treatment. rhIL-15 will be given intravenously once a day for 12 consecutive days, for a total of twelve doses of the drug. The injection of rhIL-15 will take about 30 minutes. Patients will be evaluated daily before each treatment and more frequently if necessary.
* During the 12-day treatment and for at least 42 days from the start of the treatment, patients will be closely followed for possible side effects and for tumor response. Blood will be drawn frequently for monitoring purposes, and other procedures such as chest x-rays and imaging scans will be performed to monitor the state of the tumor and the patient response to treatment.
* After completi...

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Natural killer cells in cancer biology and therapy.
   Wu SY, Fu T, Jiang YZ, Shao ZM. · · 2020 · cited 640× · PMID 32762681 · DOI 10.1186/s12943-020-01238-x
2. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer.
   Conlon KC, Lugli E, Welles HC, Rosenberg SA, et al · · 2015 · cited 564× · PMID 25403209 · DOI 10.1200/jco.2014.57.3329
3. Interleukin-15 biology and its therapeutic implications in cancer.
   Steel JC, Waldmann TA, Morris JC. · · 2012 · cited 273× · PMID 22032984 · DOI 10.1016/j.tips.2011.09.004
4. Continuous treatment with IL-15 exhausts human NK cells via a metabolic defect.
   Felices M, Lenvik AJ, McElmurry R, Chu S, et al · · 2018 · cited 210× · PMID 29415897 · DOI 10.1172/jci.insight.96219
5. The role of interleukin-15 in inflammation and immune responses to infection: implications for its therapeutic use.
   Perera PY, Lichy JH, Waldmann TA, Perera LP. · · 2012 · cited 205× · PMID 22064066 · DOI 10.1016/j.micinf.2011.10.006
6. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15.
   Ring AM, Lin JX, Feng D, Mitra S, et al · · 2012 · cited 198× · PMID 23104097 · DOI 10.1038/ni.2449
7. Molecular pathways: interleukin-15 signaling in health and in cancer.
   Mishra A, Sullivan L, Caligiuri MA. · · 2014 · cited 182× · PMID 24737791 · DOI 10.1158/1078-0432.ccr-12-3603
8. The potential and promise of IL-15 in immuno-oncogenic therapies.
   Robinson TO, Schluns KS. · · 2017 · cited 155× · PMID 28823521 · DOI 10.1016/j.imlet.2017.08.010