Clear Cell CarcinomaPhase 1NCT07072234
Phase I Study of Allogeneic Transforming Growth Factor-beta Receptor Type 2 Knockout CD70 CAR NK Cells in Treatment Refractory Clear Cell Renal Cell Carcinoma
A Phase 1 study testing Lymphodepleting chemotherapy, Dexamethasone and Fludarabine in people with Clear Cell Carcinoma and Phase 1, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
Testing an investigational cancer therapy called TGFBR-2 KO CD70 CAR NK cell therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clear Cell Carcinoma, Phase 1, Growth Factor
- What is being tested?
- Lymphodepleting chemotherapy, Dexamethasone and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Sep 2025to 1 Feb 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Presence of clinically significant ongoing Grade ≥ 2 toxicity unequivocally associated withthe previous anticancer treatment, as determined by the PI. Toxicities related to priorsurgery, 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: Participants 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 (HIV).
- Presence of active neurological disorder(s).
- Active autoimmune disease within 12 months of enrollment (excluding low-grade psoriasis or well-controlled autoimmune thyroid disease).
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- 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.
- Participants 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 Participant'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 Participant 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 NK cell infusion
- Unstable angina within ≤ 13 weeks prior to CAR 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 Participants 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.
- Participants 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 alemtuzumab within 28 days of enrollment.
- Participants receiving immunosuppressive therapy.
- Pregnant or breastfeeding.
- Has received a live vaccine within 6 weeks prior to CAR NK cell infusion. Examples of live vaccines include but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virusvaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Andrew C Johns, MD, 713-745-0138, acjohns@mdanderson.org
Andrew C Johns, MD
About this study
Testing an investigational cancer therapy called TGFBR-2 KO CD70 CAR NK cell therapy.
Read the detailed description
Primary Objective • To determine the safety, tolerability, maximum tolerated dose (MTD), and optimal celldose (OCD) of chimeric antigen receptor TGFBR-2 KO CD70 CAR NK cells in participants with advanced ccRCC.
Secondary Objectives
- To determine the antitumor activity of TGFBR-2 KO CD70 CAR NK cells. Although the clinical benefit of TGFBR-2 KO CD70 CAR NK cells has not yet been established in ccRCC, the intent of offering this treatment is to provide a possible therapeutic benefit and thus, the participants will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability.
- Conditions
- Clear Cell Carcinoma, Phase 1, Growth Factor
- Being tested
- Lymphodepleting chemotherapy, Dexamethasone, Fludarabine, Cyclophosphamate, TGFBR-2 KO CD70 CAR NK
- Medical subject headings
- Adenocarcinoma, Clear Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lymphodepleting chemotherapyDrug
Given by IV
DexamethasoneDrug
Given PO
FludarabineDrug
Given by IV
CyclophosphamateDrug
Given by IV
TGFBR-2 KO CD70 CAR NKDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| Dose-optimization phase | Experimental | Not described Receives: Drug: Lymphodepleting chemotherapy; Drug: Dexamethasone; Drug: Fludarabine; Drug: Cyclophosphamate; Drug: TGFBR-2 KO CD70 CAR NK |
| Dose-expansion phase | Experimental | Not described Receives: Drug: Lymphodepleting chemotherapy; Drug: Dexamethasone; Drug: Fludarabine; Drug: Cyclophosphamate; Drug: TGFBR-2 KO CD70 CAR NK |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTACAE) 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 posted18 Jul 2025
- Study start25 Sep 2025
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Feb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clear 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew C Johns, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07072234
- Sponsor's protocol ID
- 2025-0508
- Other IDs
- NCI-2025-04901
- Status last verified
- Apr 2026
- First submitted
- 9 Jul 2025
- Last updated
- 29 Apr 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 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Allogeneic Transforming Growth Factor-beta Receptor Type 2 Knockout CD70 CAR NK Cells in Treatment Refractory Clear Cell Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT07072234
- Acronym / sponsor ID
- 2025-0508
- Conditions
- Clear Cell Carcinoma, Phase 1, Growth Factor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 25 Sep 2025 (actual)
- Primary completion
- 1 Feb 2028 (estimated)
- Study completion
- 1 Feb 2030 (estimated)
- First posted
- 18 Jul 2025 (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.
Testing an investigational cancer therapy called TGFBR-2 KO CD70 CAR NK cell therapy.
Detailed description
Primary Objective • To determine the safety, tolerability, maximum tolerated dose (MTD), and optimal celldose (OCD) of chimeric antigen receptor TGFBR-2 KO CD70 CAR NK cells in participants with advanced ccRCC.
Secondary Objectives
- To determine the antitumor activity of TGFBR-2 KO CD70 CAR NK cells. Although the clinical benefit of TGFBR-2 KO CD70 CAR NK cells has not yet been established in ccRCC, the intent of offering this treatment is to provide a possible therapeutic benefit and thus, the participants will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose-optimization phase | Experimental | Drug: Lymphodepleting chemotherapy, Drug: Dexamethasone, Drug: Fludarabine, Drug: Cyclophosphamate, Drug: TGFBR-2 KO CD70 CAR NK |
| Dose-expansion phase | Experimental | Drug: Lymphodepleting chemotherapy, Drug: Dexamethasone, Drug: Fludarabine, Drug: Cyclophosphamate, Drug: TGFBR-2 KO CD70 CAR NK |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (25 listed)
- Presence of clinically significant ongoing Grade ≥ 2 toxicity unequivocally associated withthe previous anticancer treatment, as determined by the PI. Toxicities related to priorsurgery, 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: Participants 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 (HIV).
- 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 |
|---|---|---|
| Lymphodepleting chemotherapyGiven by IV | Drug | Dose-expansion phase, Dose-optimization phase |
| DexamethasoneGiven PO | Drug | Dose-expansion phase, Dose-optimization phase |
| FludarabineGiven by IV | Drug | Dose-expansion phase, Dose-optimization phase |
| CyclophosphamateGiven by IV | Drug | Dose-expansion phase, Dose-optimization phase |
| TGFBR-2 KO CD70 CAR NKGiven by IV | Drug | Dose-expansion phase, Dose-optimization phase |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTACAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- MD 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.
Andrew C Johns, 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 study testing Lymphodepleting chemotherapy, Dexamethasone and Fludarabine in people with Clear Cell Carcinoma and Phase 1, 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 0 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 29 Apr 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrew C Johns, MD (713-745-0138, acjohns@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (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 29 Apr 2026.