Ignite Creation Date:
2025-12-25 @ 1:15 AM
Ignite Modification Date:
2025-12-25 @ 11:24 PM
Study NCT ID:
NCT01572493
Status:
COMPLETED
Last Update Posted:
2023-03-06
First Post:
2012-04-05
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Continuous Infusion of rhIL-15 for Adults With Advanced Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I Study of a Continuous Intravenous Infusion of Recombinant Human Interleukin IL-15 (rhIL-15) in Adults With Metastatic Cancers
Status:
COMPLETED
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background:
\- 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).
Objectives:
* 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.
Eligibility:
\- Individuals at least 18 years of age with advanced cancer for which there are no effective treatments.
Design:
* 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.
\- 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).
Objectives:
* 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.
Eligibility:
\- Individuals at least 18 years of age with advanced cancer for which there are no effective treatments.
Design:
* 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.
Detailed Description:
BACKGROUND:
* Interleukin-15 (IL-15) is a stimulatory cytokine with a number of desirable immunotherapeutic features, and clinical trials evaluating recombinant human interleukin-15 (rhIL-15) are underway.
* In contrast to IL-2, IL-15 treatment does not stimulate activation-induced cell death of T-cells; potentially inhibits immunosuppressive cluster of differentiation 4 (CD4) + Interleukin-2 receptor alpha chain (CD25) + T regulatory cells, contributes to the proliferation, differentiation and activation of CD8+ T-cells and NK-cells and the maintenance of long-term cluster of differentiation 8 (CD8) + memory T-cells.
* IL-15 is active in a number of syngeneic mouse preclinical tumor models, and vaccinia-based constructs expressing IL-15 induced long-lasting, high-avidity cytotoxic CD8+ T-lymphocyte 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 intravenous (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 continuous intravenous (CIV) of rhIL-15 may have greater potential for stimulating an anticancer cellular immune response with a more manageable safety profile.
OBJECTIVES:
Primary Objective:
\- 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.
ELIGIBILITY CRITERIA:
* Patients greater than or equal to18 years-old, Eastern Cooperative Oncology Group (ECOG) performance status (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.
DESIGN:
* 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 CIV rhIL-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.
* Interleukin-15 (IL-15) is a stimulatory cytokine with a number of desirable immunotherapeutic features, and clinical trials evaluating recombinant human interleukin-15 (rhIL-15) are underway.
* In contrast to IL-2, IL-15 treatment does not stimulate activation-induced cell death of T-cells; potentially inhibits immunosuppressive cluster of differentiation 4 (CD4) + Interleukin-2 receptor alpha chain (CD25) + T regulatory cells, contributes to the proliferation, differentiation and activation of CD8+ T-cells and NK-cells and the maintenance of long-term cluster of differentiation 8 (CD8) + memory T-cells.
* IL-15 is active in a number of syngeneic mouse preclinical tumor models, and vaccinia-based constructs expressing IL-15 induced long-lasting, high-avidity cytotoxic CD8+ T-lymphocyte 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 intravenous (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 continuous intravenous (CIV) of rhIL-15 may have greater potential for stimulating an anticancer cellular immune response with a more manageable safety profile.
OBJECTIVES:
Primary Objective:
\- 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.
ELIGIBILITY CRITERIA:
* Patients greater than or equal to18 years-old, Eastern Cooperative Oncology Group (ECOG) performance status (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.
DESIGN:
* 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 CIV rhIL-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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 12-C-0113 | None | None | View |