Trial Title:
Memory-like Natural Killer (NK) Cell Therapy in Patients with Renal Cell Carcinoma or Urothelial Carcinoma
NCT ID:
NCT06318871
Condition:
Renal Carcinoma
Renal Cell Carcinoma
Urothelial Carcinoma
Chromophobe Renal Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Renal Cell
Carcinoma, Transitional Cell
Kidney Neoplasms
Interleukin-2
Conditions: Keywords:
Renal Carcinoma
Renal Cell Carcinoma
Advanced Clear Renal Cell Carcinoma
Urothelial Carcinoma
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Cytokine Induced Memory-like Natural Killer (CIML NK) Cells
Description:
Autologous, cytokine induced memory-like natural killer cells, via intravenous (into the
vein) infusion per protocol.
Arm group label:
Dose Level -1: CIML NK + low dose IL-2
Arm group label:
Dose Level 0: CIML NK + low dose IL-2
Other name:
NK Cells
Intervention type:
Drug
Intervention name:
Interleukin-2 (IL-2)
Description:
Interleukin-2 (aldesleukin, IL-2) will be used to support natural killer cell
proliferation and activity
Arm group label:
Dose Level -1: CIML NK + low dose IL-2
Arm group label:
Dose Level 0: CIML NK + low dose IL-2
Summary:
The goal of this research study is to establish the safety and then to explore the
effectiveness of infusing the combination of cytokine-induced memory-like (CIML) natural
killer (NK) cells, a type of immune cell in the blood that is collected and bathed in
special proteins to help identify and treat curtained advanced cancers, combined with low
dose IL-2, which is a cytokine that activates immune cells, in advanced clear cell renal
cell carcinoma and urothelial carcinoma.
Names of the study therapies involved in this study are/is:
- CIML NK cell therapy (a NK cell therapy)
- IL-2 (a type of cytokine)
Detailed description:
The purpose of this research study is to obtain information on the feasibility of CIML NK
cell therapy with IL-2 to treat advanced clear cell renal cell carcinoma and urothelial
carcinoma. This is the first time that the specific combination of CIML NK cells and IL-2
will be given to humans.
The U.S. Food and Drug Administration (FDA) has not approved CIML NK cells post
Maintenance Culture as a treatment for renal cell carcinoma or urothelial carcinoma.
The FDA has approved IL-2 as a treatment for renal cell carcinoma but the dose used will
be lower than the approved dose, as IL-2 is intended to support the CIML NK cells.
This research study involves screening for eligibility, collection of natural killer (NK)
cells in a process called leukapheresis, treatment visits, X-rays, Computerized
Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron Emission
Tomography (PET) scans, blood tests, urine tests, echocardiograms, electrocardiograms
(ECGs), and tumor biopsies.
Participants will be in this research study for up to 5 years from the CIML NK cell
infusion.
It is expected that about 5 people will take part in this research study.
This research is supported by a grant from the Kidney Cancer Association.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed, advanced or metastatic clear cell renal
cell carcinoma, chromophobe renal cell carcinoma, or urothelial carcinoma. The
presence of rhabdoid or sarcomatoid differentiation is permitted if a clear cell or
urothelial carcinoma component is also present.
- Participants must have measurable disease, defined as at least one lesion that can
be accurately measured in at least one dimension (longest diameter to be recorded
for nonnodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest
x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See
Section 11 (Measurement of Effect) for the evaluation of measurable disease.
- Age ≥18 years. Because no dosing or adverse event data are currently available on
the use of CIML NK cells in participants <18 years of age, children are excluded
from this study, but would be eligible for future pediatric trials.
- Participants with clear cell RCC or UC must have progression after prior treatment
failure with at least one PD-1/PD-L1 immune checkpoint inhibitor that is FDA
approved for treatment of UC or RCC as of the date of informed consent.
- Patients with renal cell carcinoma should also have prior treatment failure with at
least one prior VEGFR TKI, or contraindication to VEGFR TKIs as determined by the
treating clinician. Patients with urothelial carcinoma should have either prior
treatment failure with ≥1 prior cytotoxic chemotherapy or antibody-drug conjugate.
There is no limit on the number of prior lines of therapy received.
- ECOG performance status ≤1 (Karnofsky ≥80%, see Appendix A).
- Participants must meet the following organ and marrow function as defined below:
- absolute neutrophil count ≥1,000/mcL
- hemoglobin ≥8g/dL (prior transfusion permitted)
- platelets ≥75,000/mcL
- total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) except if
secondary to Gilbert's, then < 3 x ULN
- AST(SGOT)/ALT(SGPT) ≤3.0 × institutional ULN
- creatinine ≤ 2.0 OR
- glomerular filtration rate (GFR) ≥40 mL/min/1.73 m2 for participants with
creatinine levels above institutional ULN.
- oxygen saturation ≥ 90% on room air
- left ventricular ejection fraction > 40%
- No laboratory evidence of ongoing hemolysis in opinion of investigator
- Participants with known history or current symptoms of cardiac disease, or history
of treatment with cardiotoxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association Functional Classification. To
be eligible for this trial, participants should be class 2B or better.
- Willing to provide blood and tissue from diagnostic biopsy
- Negative serum or urine pregnancy test at screening for women of childbearing
potential. Highly effective contraception for female subjects of childbearing
potential throughout the study if the risk of conception exists.
- Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
- Participants who have had anti-tumor chemotherapy or other investigational agents
within 2 weeks prior to enrollment(4 weeks for nitrosoureas or mitomycin C), or
immunotherapy within 4 weeks prior.
- Persisting toxicity related to prior therapy (NCI CTCAE Grade > 1); however,
alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety
risk based on investigator's judgment are acceptable.
- Prior recipients of organ transplantation.
- Participants who are receiving any other investigational agents.
- Participants with leptomeningeal disease are excluded from this clinical trial due
to their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events. Patients with treated brain metastases are eligible if imaging has shown
stability over at least 4 weeks.
- Autoimmune disease: patients with a history of inflammatory bowel disease, including
ulcerative colitis and Crohn disease, are excluded from this study, as are patients
with a history of active autoimmune disease (e.g., rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
vasculitis [Wegener's granulomatosis]) and motor neuropathy considered of autoimmune
origin (e.g., Guillain-Barre syndrome and myasthenia gravis). Patients with diabetes
type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring
immunosuppressive treatment are eligible.
- Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6
months prior to enrollment), unstable angina, congestive heart failure (≥ New York
Heart Association Classification Class II), or unstable cardiac arrhythmia requiring
medication. Patients with rate controlled atrial fibrillation / atrial flutter on
stable medical therapy are eligible.
- Other uncontrolled intercurrent illness including, but not limited to, ongoing or
active infection requiring systemic therapy, or uncontrolled psychiatric conditions
including recent (within the past year) or active suicidal ideation or behavior, or
other psychiatric illness/social situations that would limit compliance with study
requirements, or laboratory abnormalities that may increase the risk associated with
study participation or study treatment administration or may interfere with the
interpretation of study results and, in the judgment of the investigator, would make
the patient inappropriate for entry into this study.
- Participants with known additional malignancy that is progressing or requires active
treatment, or history of other malignancy within 2 years of enrollment, with the
exception of cured basal cell or squamous cell carcinoma of the skin, superficial
bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix,
or other non-invasive or indolent malignancy, or cancers from which the patient has
been disease-free for > 1 year after treatment with curative intent.
- No systemic corticosteroid therapy (≥ 10 mg of prednisone or equivalent dose of
systemic steroids for non-autoimmune indications for at least 2 weeks prior to
enrollment).
- Pregnant women are excluded from this study because of the unknown teratogenic risk
of CIML NK cells and N-803 and with the potential for teratogenic or abortifacient
effects by fludarabine/cyclophosphamide chemotherapy regimen. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with CIML NK cells and N-803, breastfeeding should be
discontinued if the mother is treated on this study. For this reason, women of
child-bearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study or 12 months after
last treatment, she should inform her treating physician immediately. Men treated or
enrolled on this protocol must also agree to use adequate contraception prior to the
study, for the duration of study participation, and 12 months after completion of
the last CIML NK cell and/or last N-803 administration.
- Participants with history of positive HIV testing are ineligible because of the
potential for pharmacokinetic interactions with anti-retroviral agents and the
treatments used in this study. In addition, these participants are at increased risk
of lethal infections when treated with marrow-suppressive therapy.
- Individuals with Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at
screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening
test positive) are ineligible as they are at increased risk of lethal
treatment-related hepatotoxicity.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to N-803 or other agents used in study.
- Receipt of a live vaccine within 2 weeks prior to enrollment.
- Known prior severe allergic/anaphylactic reactions to murine-based antibody therapy
or iron dextran, as the CIML NK cell product contains similar reagents at end of
manufacturing/infusion.
- Prior history of Grade 2 or higher hemolytic anemia (>/= 2g decrease in
hemoglobin plus laboratory evidence of hemolysis) from any cause.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Wenxin Xu, MD
Phone:
(617) 632-6534
Email:
wenxin_xu1@dfci.harvard.edu
Contact backup:
Last name:
Wenxin Xu, MD
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Wenxin Xu, MD
Phone:
(617) 632-6534
Email:
Wenxin_Xu1@dfci.harvard.edu
Contact backup:
Last name:
Wenxin Xu, MD
Start date:
August 28, 2024
Completion date:
May 28, 2030
Lead sponsor:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Kidney Cancer Association
Agency class:
Other
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06318871