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

NCT05703854 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2021-0443NCI-2023-00469
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Renal Cell Carcinoma; Advanced Mesothelioma; Advanced Osteosarcoma

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (1)

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.

Drug: CAR.70/IL15-transduced CB-derived NK cells; Drug: Fludarabine phosphate; Drug: Cyclophosphamide

Interventions

CAR.70/IL15-transduced CB-derived NK cells DRUG

Given by IV (vein)

Chemotherapy and NK Cell Infusion

Fludarabine phosphate DRUG

Given by IV (vein)

Also known as: Fludarabine, Fludara®

Chemotherapy and NK Cell Infusion

Cyclophosphamide DRUG

Given by IV (vein)

Also known as: Cytoxan®, Neosar®

Chemotherapy and NK Cell Infusion

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify 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 ≥ 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.
• 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.

You may not qualify 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 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).
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

fludarabine phosphate; fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• David Hong, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Hong, MD

CONTACT

(713) 563-5844; dshong@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: January 30, 2023
• Study Start: March 29, 2023
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

US (1)