Advanced Renal Cell CarcinomaPhase 1/2NCT05703854
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
A Phase 1/2 study testing CAR.70/IL15-transduced CB-derived NK cells, Fludarabine phosphate and Cyclophosphamide in people with Advanced Renal Cell Carcinoma and Advanced Mesothelioma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 16 to 80 years
- Conditions the study is for
- Advanced Renal Cell Carcinoma, Advanced Mesothelioma, Advanced Osteosarcoma
- What is being tested?
- CAR.70/IL15-transduced CB-derived NK cells, Fludarabine phosphate and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2023to 30 Sep 2027
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to 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 renal cell carcinoma and mesothelioma, or ≥ 1% for osteosarcoma.
- 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.
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- 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 Syndrome. No history of liver cirrhosis and no ascites.
- 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 serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with anti-arrhythmic medication)
- Pulmonary: No clinically significant pleural effusion (per principal investigator [PI] judgement), and baseline oxygen saturation ≥ 92% on room air. Subjects with active interstitial lung disease (ILD)/pneumonitis requiring treatment with systemic steroids will be excluded.
- 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 limit of the therapeutic range for intended use.
- 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 female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence. Female patients who become pregnant or suspect pregnancy must immediately notify their doctor. Females patients who become pregnant will be taken off study. Men who are able to have children must use effective birth control while on the study therapy. Acceptable forms of birth control for male patients include: condom with spermicide or abstinence. If the male patient fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
- 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 screening.
- Signed consent to long-term follow-up on protocol PA17-0483.
- Disease-specific inclusion criteria
- 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 tyrosine kinase inhibitor. Prior progression on a PD-1 or PD-L1 checkpoint inhibitor should be unequivocal.
- 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 a PD-1 or PD-L1 checkpoint inhibitor should be unequivocal.
- 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 chemotherapy regimen based on anthracycline, if no contra-indication to this class of drug. Must have histologic verification of their disease at diagnosis or at relapse.
- 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 (surgery, chemotherapy), excluding lung metastases amenable to surgical resection.
- Patients must have evaluable or measurable disease per the RECIST v1.1 at enrollment.
Who cannot join
- 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 immune checkpoint inhibitors and chemotherapy should be resolved to Grade 1 or below prior to lymphodepletion.
- 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 bacterial pharyngitis are permitted if responding to active treatment.
- 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 cannot be changed/temporarily suspended, according to PI evaluation.
- Presence of active neurological disorder(s).
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- 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 basal or squamous cell carcinomas of the skin, or active non-life-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but are not limited to: urothelial cancer Grade Ta or T1 and adenocarcinoma of the prostate treated by active surveillance.
- 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 each other. The patient should be reclining for 5 minutes prior to ECGs. Local readings may be used for this exclusion criterion.
- 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 daily (physiological substitutive doses are allowed).
- Received antithymocyte globulin within 14 days or Campath within 28 days of enrollment.
- Patients receiving immunosuppressive therapy.
- Pregnant or breastfeeding.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II 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
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.
Read the detailed description
Primary Objective:
- To determine the safety, tolerability, and optimal cell dose of chimeric antigen receptor (CAR).70/interleukin (IL)15-transduced cord blood (CB)-derived natural killer (NK) cells in patients with advanced renal cell carcinoma, advanced mesothelioma, and advanced osteosarcoma.
- To determine the antitumor activity of CAR.70/IL15-transduced CB-derived NK cells. Although the clinical benefit of CAR.70/IL15-transduced CB-derived NK cells has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit and thus, the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. Efficacy will be determined in each of the three cohorts.
Secondary Objectives:
- To quantify the persistence of infused allogeneic donor CAR-transduced CB-derived NK cells in the recipient.
- To conduct comprehensive immune reconstitution studies.
- To obtain preliminary data on quality of life and patient experience.
- Being tested
- CAR.70/IL15-transduced CB-derived NK cells, Fludarabine phosphate, Cyclophosphamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR.70/IL15-transduced CB-derived NK cellsDrug
Given by IV (vein)
Also called Fludarabine, Fludara®
Given by IV (vein)
CyclophosphamideDrug
Also called Cytoxan®, Neosar®
Given by IV (vein)
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy and NK Cell Infusion | Experimental | Participants will be assigned to a dose level of NK cells. A computer will decide by chance which of the dose level you will receive, and this will not be based on the doctor's or patient's decision. Up to 5 dose levels of NK cells will be tested. Each new patient will receive a different dose. If any dose shows to be not tolerable, this dose and the higher doses will not be given anymore. Receives: Drug: CAR.70/IL15-transduced CB-derived NK cells; Drug: Fludarabine phosphate; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2023
- Study start29 Mar 2023
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Why it stopped: PI Request
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Renal Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Hong, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05703854
- Sponsor's protocol ID
- 2021-0443
- Other IDs
- NCI-2023-00469
- Status last verified
- Jul 2026
- First submitted
- 17 Jan 2023
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II 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
- Acronym / sponsor ID
- 2021-0443
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: PI Request
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 29 Mar 2023 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 30 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Primary Objective:
- To determine the safety, tolerability, and optimal cell dose of chimeric antigen receptor (CAR).70/interleukin (IL)15-transduced cord blood (CB)-derived natural killer (NK) cells in patients with advanced renal cell carcinoma, advanced mesothelioma, and advanced osteosarcoma.
- To determine the antitumor activity of CAR.70/IL15-transduced CB-derived NK cells. Although the clinical benefit of CAR.70/IL15-transduced CB-derived NK cells has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit and thus, the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. Efficacy will be determined in each of the three cohorts.
Secondary Objectives:
- To quantify the persistence of infused allogeneic donor CAR-transduced CB-derived NK cells in the recipient.
- To conduct comprehensive immune reconstitution studies.
- To obtain preliminary data on quality of life and patient experience.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy and NK Cell Infusion | Experimental | Drug: CAR.70/IL15-transduced CB-derived NK cells, Drug: Fludarabine phosphate, Drug: CyclophosphamideParticipants will be assigned to a dose level of NK cells. A computer will decide by chance which of the dose level you will receive, and this will not be based on the doctor's or patient's decision. Up to 5 dose levels of NK cells will be tested. Each new patient will receive a different dose. If any dose shows to be not tolerable, this dose and the higher doses will not be given anymore. |
Who may qualify
- Ages
- 16 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (35 listed)
- 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 renal cell carcinoma and mesothelioma, or ≥ 1% for osteosarcoma.
- 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.
Key exclusion criteria (26 listed)
- 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 immune checkpoint inhibitors and chemotherapy should be resolved to Grade 1 or below prior to lymphodepletion.
- 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 bacterial pharyngitis are permitted if responding to active treatment.
- 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 cannot be changed/temporarily suspended, according to PI evaluation.
- Presence of active neurological disorder(s).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAR.70/IL15-transduced CB-derived NK cellsGiven by IV (vein) | Drug | Chemotherapy and NK Cell Infusion |
| Fludarabine phosphateAlso: Fludarabine, Fludara®Given by IV (vein) | Drug | Chemotherapy and NK Cell Infusion |
| CyclophosphamideAlso: Cytoxan®, Neosar®Given by IV (vein) | Drug | Chemotherapy and NK Cell Infusion |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Time frame: through study completion; an average of 1 year.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Hong, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CAR.70/IL15-transduced CB-derived NK cells, Fludarabine phosphate and Cyclophosphamide in people with Advanced Renal Cell Carcinoma and Advanced Mesothelioma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 35 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: paused, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 (time frame: through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.