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New treatment option for Advanced Renal Cell Carcinoma
Official title Study of CAR.70-engineered IL15-transduced Cord Blood-derived NK Cells in Conjunction With Lymphodepleting Chemotherapy for the Management of Advanced Renal Cell Carcinoma, Mesothelioma and Osteosarcoma
ClinicalTrials.gov ID: NCT05703854
What this study is testing
What is CAR.70/IL15-transduced CB-derived NK cells?
CAR.70/IL15-transduced CB-derived NK cells is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for advanced renal cell carcinoma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- To find a recommended dose of donated NK cells that can be given with lymphodepleting chemotherapy to patients with advanced renal cell carcinoma, mesothelioma, or osteosarcoma. The effects of this therapy will also be studied.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 16 to 80
You may be able to join if
- Patients must meet the following criteria for study entry:
- Patients with advanced clear cell renal cell carcinoma, osteosarcoma or mesothelioma, with an expression of CD70 in the pre-enrollment tumor sample ≥...
- Patients must meet disease-specific eligibility criteria (see below).
- Patients must be at least 2 weeks from last cytotoxic chemotherapy, tyrosine kinase inhibitors or other targeted therapies at the time of...
- Patients must be at least 3 months from any cell therapy for malignancy.
You likely can't join if
- Patients who meet any of the following criteria will be excluded from study entry:
- Presence of clinically significant ongoing Grade ≥ 2 toxicity unequivocally associated with the previous anticancer treatment, as determined by the...
- Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management or not responding to appropriate therapy. Note...
- Known active hepatitis B or C.
- Known human immunodeficiency virus with detectable viral load. Patients with undetectable viral load may be excluded in case the antiretroviral drug...
- Presence of active neurological disorder(s).
See the full eligibility criteria
Who can join
- Patients must meet the following criteria for study entry:
- Patients with advanced clear cell renal cell carcinoma, osteosarcoma or mesothelioma, with an expression of CD70 in the pre-enrollment tumor sample ≥ 10% measured by immunohistochemistry or flow cytometry for clear cell...
- Patients must meet disease-specific eligibility criteria (see below).
- Patients must be at least 2 weeks from last cytotoxic chemotherapy, tyrosine kinase inhibitors or other targeted therapies at the time of administration of lymphodepleting chemotherapy.
- Patients must be at least 3 months from any cell therapy for malignancy.
- Localized radiotherapy to 1 or more disease sites is allowed prior to the lymphodepleting chemotherapy, provided that there are additional measurable non-irradiated disease sites.
- Eastern Cooperative Oncology Group performance status 0 or 1 (Performance level as measured by Karnofsky for patients \> 16 years of age or Lansky for patients ≤ 16 years of age, see Appendix A).
- Adequate organ function at screening, as defined by the following:
- Renal: Serum creatinine ≤ 1.5 mg/dL or estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation) ≥30 ml/min/1.73 m2
- Hepatic: alanine transaminase (ALT)/aspartate transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if documented liver metastases, total bilirubin ≤ 1.5 mg/dL or ≤ 3.0 mg/dL for patients with Gilbert's...
- Cardiac: Cardiac ejection fraction ≥ 50%, no clinically significant pericardial effusion as determined by echocardiogram (ECHO) or multigated acquisition (MUGA) scan, and no symptomatic cardiac disease or history of...
- Pulmonary: No clinically significant pleural effusion (per principal investigator [PI] judgement), and baseline oxygen saturation ≥ 92% on room air. people with active interstitial lung disease (ILD)/pneumonitis...
- Hematological: absolute neutrophil count (ANC) ≥ 1000/mm3, platelet count ≥ 75,000/mm3, and hemoglobin ≥ 8 g/dL. For patients with human immunodeficiency virus infection, CD4+ T-cell (CD4+) counts must be ≥ 350 cells/uL.
- Coagulation: International normalized ratio (INR) ≤ 1.5 ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 ULN. Patients on therapeutic doses of anticoagulation medication must have INR and/or aPTT ≤ the upper...
- Able to provide written informed consent and if applicable pediatric assent.
- Aged 16-80 years.
- Weight ≥40 kg.
- All male and female patients who are able to have children must practice effective birth control while on study therapy and for up to 3 months post completion of study therapy. Acceptable forms of birth control for...
- Negative serum or urine beta human chorionic gonadotropin pregnancy test for females of childbearing potential (defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females) at...
- Signed consent to long-term follow-up on protocol PA17-0483. Disease-specific Renal Cell Carcinoma
- Patients must have a histologically confirmed diagnosis of Stage 4 RCC with a clear cell component.
- Patients must have received at least 1 prior line of therapy for recurrent or metastatic disease, including both PD-1/programmed cell death-ligand 1 immunotherapy and anti-angiogenic-directed treatment, such as a...
- Patients must have at least 1 measurable lesion \>10 mm on computed tomography (CT) per the RECIST v1.1.
- Mesothelioma
- Patients must have pathologically confirmed mesothelioma
- Patients must have progressive, recurrent, or refractory disease (local recurrence) or new disease after all curative measures, including first-line chemotherapy, targeted therapy, and radiotherapy. Prior progression on...
- Patients must have measurable or evaluable disease per the RECIST v1.1 at enrollment.
- Osteosarcoma
- Patients must have histologically confirmed osteosarcoma that is recurrent or refractory and for which standard curative measures do not exist or are no longer effective. The patient must have received at least one...
- Patients must have at least:
- Progressive, recurrent, or refractory disease (local recurrence) or new disease after all curative measures, including first-line chemotherapy, targeted therapy, and radiotherapy.
- Evidence of persistent and progressive disease on imaging, which may include fludeoxyglucose F-18 positron emission tomography (PET)-avid metastasis, that has failed to achieve CR to upfront conventional therapy...
- Patients must have evaluable or measurable disease per the RECIST v1.1 at enrollment.
What rules you out
- Patients who meet any of the following criteria will be excluded from study entry:
- Presence of clinically significant ongoing Grade ≥ 2 toxicity unequivocally associated with the previous anticancer treatment, as determined by the PI. Toxicities related to prior surgery, radiation, prior systemic...
- Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management or not responding to appropriate therapy. Note: Patients with simple urinary tract infection and uncomplicated...
- Known active hepatitis B or C.
- Known human immunodeficiency virus with detectable viral load. Patients with undetectable viral load may be excluded in case the antiretroviral drug cannot be co-administered with the lymphodepleting chemotherapy and...
- Presence of active neurological disorder(s).
- Active autoimmune disease within 12 months of enrollment (excluding low-grade psoriasis or well-controlled autoimmune thyroid disease).
- Amyloidosis or POEMS syndrome.
- Symptomatic or uncontrolled central nervous system involvement or signs of cord compression. In the case radiation therapy is indicated, the washout must be at least 14 days.
- Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post resection or post radiotherapy) carcinoma of the cervix or...
- Presence of any other serious medical condition that may endanger the patient at investigator's discretion, including but not limited to:
- New York Heart Association Class III or IV heart failure
- Myocardial infarction or stroke ≤ 26 weeks prior to CAR.70 NK cell infusion
- Unstable angina within ≤ 13 weeks prior to CAR.70 NK cell infusion unless the underlying disease has been corrected by procedural intervention (e.g., stent, bypass)
- Severe aortic stenosis
- Uncontrolled arrhythmia. PI approval is required for patients with arrhythmia who may be included as an exception.
- Congenital long QT syndrome. PI approval is required.
- Documentation, during the screening process, of a QTc \> 470 milliseconds by Fredericia criteria (QTcF) based on the average of 3 electrocardiograms (ECGs) taken approximately 1 minute apart and all within 10 minutes of...
- Major surgery \< 4 weeks prior to first dose of lymphodepleting chemotherapy.
- Concomitant use of other investigational agents.
- Concomitant use of other anticancer agents.
- Previously received any anti-CD70 therapy.
- Patients receiving systemic steroid therapy at time of enrollment, with an exception for topical, ocular, intranasal, and inhaled corticosteroids, or systemic corticosteroids at an equivalent dose ≤ 10 mg of prednisone...
- Received antithymocyte globulin within 14 days or Campath within 28 days of enrollment.
- Patients receiving immunosuppressive therapy.
- Pregnant or breastfeeding.
The study team makes the final eligibility decision.
Where it's taking place
- Houston, Texas, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 16 years to 80 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Houston, Texas, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.