Phase 1
Completed N=38
Continuous Infusion of rhIL-15 for Adults With Advanced Cancer
Lymphoma · Carcinoma
Source: ClinicalTrials.gov NCT01572493 ↗
Enrolled (actual)
38
Serious AEs
36.8%
Results posted
Mar 2023
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 10 Day Dosing — 2 mcg/kg/day
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 10 Day Dosing |
2 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Recombinant Human Interleukin-15 (rhIL-15) for 5 Day Dosing |
NA | — |
| PRIMARY Number of Participants With Grades 3, 4 or 5 Dose-Limiting Toxicity (DLT) Related to Study Drug |
2; 0; 0; 1; 0; 0 | — |
| SECONDARY Clinical Response Rate |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Time to Progression (TTP) |
74; 54; 29; 77; 68; 6 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Recombinant Human Interleukin-15 (rhIL-15) |
51; 59; 116; 1413; 5662; 26852 | — |
| SECONDARY Concentration of Drug in Plasma at Steady State (Css) |
44.5; 48.5; 73.2; 489; 2020; 9562 | — |
| SECONDARY Area Under the Curve (AUClast) |
7756; 10907; 20798; 187453; 321747; 262651 | — |
| SECONDARY Inflammatory Cytokines |
0.38; 0.24; 9.8; 0.86; 0.34; 0.24 | — |
Eligibility Criteria
- INCLUSION CRITERIA
- Age greater than or equal to 18 years.
- Patients must have histologically confirmed (by the National Cancer Institute (NCI) Pathology Department) solid tumor malignancy or lymphoma that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are associated with minimal patient survival benefit (as defined the Metabolism Branch physicians or if the patient refuses standard of care treatment). Enrollment of patients with tumors that can be safely biopsied is encouraged.
- Patients must have evaluable or measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan.
- Patients must have recovered to 60% of predicted on pulmonary function tests.
- Serum creatinine of less than or equal to 1.5 X the upper limit of normal.
- Aspartate aminotransferase (AST) and alanine aminotransferase (AST) < 2.5 x the upper limit of normal.
- Absolute neutrophil count greater than or equal to 1,500/mm(3) and platelets greater than or equal to 100,000/mm(3).
- Karnofsky performance status greater than or equal to 70% or Eastern Cooperative Oncology Group (ECOG) less than or equal to 1
- Subjects with inactive central nervous system (CNS) metastasis are eligible. Inactive CNS metastasis is defined as: no signs of cerebral edema after successful definitive treatment of brain metastases (surgical resection, whole brain irradiation, stereotactic radiation therapy, or a combination of these) with stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month after completion of treatment.
EXCLUSION CRITERIA
- Patients who have received any systemic corticosteroid therapy within 3 weeks prior to the start of therapy with the exception of physiological replacement doses of cortisone acetate or equivalent.
- Patients who have received any cytotoxic therapy, immunotherapy, antitumor vaccines, monoclonal antibodies or major surgery in the 4 weeks prior to the start of the study.
- Life expectancy of less than 3 months.
- Patients with more than 30% replacement of hepatic parenchyma by tumor or any history of drug related hepatic encephalopathy.
- History of complex ventricular or supraventricular arrhythmias
- Documented human immunodeficiency virus (HIV), active bacterial infections, active or chronic hepatitis B, or hepatitis C infection.
- A positive hepatitis B serology indicative of previous immunization (i.e., hepatitis B surface antigen (HBsAb) positive and hepatitis B core antibody (HBcAb) negative), or a fully resolved acute hepatitis B infection is not an exclusion criterion.
- A positive hepatitis C serology is an exclusion criterion.
- Concurrent anticancer therapy (including other investigational agents), with the exception of hormone therapy for prostate cancer.
- Active central nervous system (CNS) metastases (inactive CNS metastases are defined).
- History of severe asthma or presently on chronic inhaled corticosteroid medications (patients with a history of mild asthma controlled with inhaled bronchodilators are eligible).
- History of autoimmune disease, with the exception of an autoimmune event associated with prior ipilimumab (anti-cluster of differentiation 152 (CTLA-4) therapy that has been completely resolved for more than 4 weeks.
- Inability or refusal to practice effective contraception during therapy or the presence of pregnancy or active breastfeeding (men and women of childbearing potential must use an effective method of birth control or abstinence during treatment and for 4 months after completion of treatment).
- Cognitive impairment, history of medical or psychiatric disease, other uncontrolled intercurrent illness, active substance abuse, or so
Data sourced from ClinicalTrials.gov (NCT01572493). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.