Continuous Infusion of rhIL-15 for Adults With Advanced Cancer
- People with cancer can have a weak immune system as a result of the cancer itself, or from prior treatments. . Still, treatments that stimulate the immune system have been shown to be effective against a number of different cancers. Recombinant human interleukin-15 (rhIL-15) is a drug that is designed to boost the immune system. Researchers are interested in seeing if rhIL-15 can strengthen the immune system's response against cancer. The drug will be given through a vein without a break for 10 days (240 hours).
- To see rhIL-15 given as a continuous infusion over 10 days can be used to treat advanced cancer
- Identify the side effects associated with this treatment.
- Individuals at least 18 years of age with advanced cancer for which there are no effective treatments.
- Participants screening procedures will include a physical exam and medical history, laboratory (blood) tests and x-rays (Imaging studies) to determine suitability for the protocol. --Appropriate participants with easily accessible tumor deposits may also be asked to have one pretreatment and one post (cycle 1) treatment tumor biopsy. .
- Eligible participants will be admitted to the hospital for the rhIL-15 treatment and will spend about 12 days in the hospital. .
- Participants will receive one 10 day infusion each cycle (about every 42 days) for as long as there are no serious side effects and the disease does not progress.
- Participants will continue treatment as long as imaging studies show that the tumor continues to shrink or for two additional cycles after it has disappeared from the x-rays to make that the cancer is completely gone.
- Participants who stop treatment for side effects or because their tumor did not shrink or stopped responding to the treatment will continue to have follow-up visits to monitor the outcome of the rhIL-15 treatment until there is evidence their cancer has progress or they begin another treatment.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of a Continuous Intravenous Infusion of Recombinant Human Interleukin IL-15 (rhIL-15) in Adults With Metastatic Cancers|
- MTD and DLT [ Time Frame: After one cycle ] [ Designated as safety issue: Yes ]
- Measure response rate [ Time Frame: After completion of treatment ] [ Designated as safety issue: No ]
- Measure time to progression [ Time Frame: When patient has progressive disease ] [ Designated as safety issue: No ]
- Measure PKs [ Time Frame: After completion of treatemnt ] [ Designated as safety issue: No ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||April 2020|
|Estimated Primary Completion Date:||April 2018 (Final data collection date for primary outcome measure)|
IL-15 IV for first 10 days of each cycle
Biological: rh IL-15
IL-15 IV for first 10 days of each cycle
IL-15 IV for first 5 days of each cycle
Biological: rh IL-15
rh IL-15 for first 5 days of each cycle
- Interleukin-15 (IL-15) is a stimulatory cytokine with a number of desirable immunotherapeutic features, and clinical trials evaluating recombinant human (rh) IL-15 are underway.
- In contrast to IL-2, IL-15 treatment does not stimulate activation-induced cell death of Tcells; potentially inhibits immunosuppressive CD4+CD25+ T regulatory cells, contributes to the proliferation, differentiation and activation of CD8+ T-cells and NK-cells and the maintenance of long-term CD8+ memory T-cells.
- IL-15 is active in a number of syngeneic mouse preclinical tumor models, and vacciniabased constructs expressing IL-15 induced long-lasting, high-avidity cytotoxic CD8+ Tlymphocyte response that appears to be more effective than similar IL-2 expressing vaccines.
- Pharmacology/toxicology (pharm/tox) experiments in non-human primate (NHP) rhesus macaques and preliminary results from the first-in-human phase I trial examining rhIL-15 given as an IV bolus (IVB) for 12 consecutive days indicate significant stimulation and expansion of NK-cells and CD8+ T-cells.
- rhIL-15 given as an IVB at 1 mcg/kg dose level appears to be well tolerated despite the presence of some common cytokine-related side effects indicating that 0.1 mcg/kg/day is an appropriate initial dose level for a phase I safety trial of continuous intravenous infusion (CIV) of rhIL-15.
- Comparison of the pharmacokinetic and immunologic assessments from the IVB phase I trial with the data from both sets of NHP pharm/tox experiments suggest that CIV of rhIL-15 may have greater potential for stimulating an anticancer cellular immune response with a more manageable safety profile.
- Determine the safety, toxicity profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of rhIL-15 administered as a CIV for 10 consecutive days (240 hours) in subjects with metastatic unresectable cancers for which curative or palliative measures either do not exist or are not associated with a survival advantage.
- Patients greater than or equal to18 years-old, ECOG PS less than or equal to 1, with pathologically confirmed metastatic unresectable cancers for which curative or palliative measures either do not exist or are not associated with a survival advantage.
- Patients with measurable or evaluable disease, normal organ and bone marrow function.
- This is a single-institution, open-label, non-randomized 3 + 3 design phase I dose escalation study.
- Groups of 3 to 6 subjects will receive CIV rhIL-15 at doses of 0.1, 0.25, 0.5 1, 2, 4, 6 and 8 mcg/kg/day for 10 days provided that DLT has not been observed.
- After assessments of the 10-day dosing cohorts have been completed, new groups of 3 to 6 subjects will receive CIVrhIL-15 at doses of 3, 4 and 5 mcg/kg/day for 5 days provided that a DLT has not been observed.
- Patients with evidence of response and the absence of significant toxicities will be eligible for repeat cycles of treatment.
- Samples for correlative studies will be obtained prior to treatment and at specific times points during and after treatment to assess pharmacokinetics of rhIL-15, the effect of rhIL-15 on immune cell subset populations and pro-inflammatory cytokine levels in the peripheral blood and for the development of neutralizing anti-rhIL-15 antibodies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01572493
|Contact: Maureen E Edgerly, R.N.||(240) email@example.com|
|Contact: Kevin C Conlon, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Kevin C Conlon, M.D.||National Cancer Institute (NCI)|