Gene Modified Immune Cells After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors

March 13, 2026 updated by: Anusha Kalbasi

Phase I Dose Escalation Study of Systemically Administered IL13Ra2 Chimeric Antigen Receptor (CAR) T Cells After a Nonmyeloablative Conditioning Regimen in Patients With Metastatic Melanoma and Other Solid Tumors

This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the safety of systemic administration of IL13Ralpha2-redirected CAR T cells, including determination of the maximum tolerated dose (MTD).

SECONDARY OBJECTIVES:

I. Clinical response. II. Determine the infiltration of IL13Ralpha2 CAR T cells into the tumor. III. Determine the persistence of IL13Ralpha2 CAR T cells in the peripheral blood.

EXPLORATORY OBJECTIVES:

I. Evaluate the induction of endogenous anti-tumor T cell responses in patients receiving IL13Ralpha2 CAR T cell therapy.

II. Assess for the occurrence of cytokine release syndrome in patients receiving IL13Ralpha2 CAR T cells by evaluating plasma cytokine levels.

OUTLINE: This is a dose-escalation study of IL13Ralpha2-specific hinge-optimized 4-1BB-co-stimulatory CAR/truncated CD19-expressing autologous TN/MEM cells (IL13Ralpha2 CAR T cells) followed by a dose-expansion study.

Patients may receive cyclophosphamide intravenously (IV) over 60 minutes on days -5 to -3 and fludarabine phosphate IV over 15-30 minutes on days -5 to -2. Patients then receive IL13Ralpha2 CAR T cells IV on day 0. Patients also undergo biopsy at baseline and on study, computed tomography (CT), or positron emission tomography (PET) and CT scan at screening and on study, magnetic resonance imaging (MRI) throughout the trial, and collection of blood samples throughout the trial. Patients with disease progression may receive a second cycle with an infusion of IL13Ralpha2 CAR T cells.

After completion of study treatment, patients are followed every 2-3 months for 2 years, every 6 months for 3 years, then every year for at least 15 years.

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Yan Xing, MD, PhD
      • Los Angeles, California, United States, 90095
        • Recruiting
        • UCLA / Jonsson Comprehensive Cancer Center
        • Principal Investigator:
          • Antoni Ribas, MD, PhD
        • Contact:
      • Stanford, California, United States, 93405
        • Recruiting
        • Stanford Cancer Institute
        • Principal Investigator:
          • Allison Betof Warner, MD, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed malignancy that is considered surgically incurable with either:

    • Stage IIIC melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis
    • Stage IV melanoma including patients with known brain metastases
    • Other metastatic, non-central nervous system (CNS) solid tumor relapsed or refractory after all standard-of-care systemic therapies for which the patient is eligible
  • Confirmed IL13Ralpha2 tumor expression by immunohistochemistry (immunohistochemical assay [IHA] H-Score >= 50 in at least 10% of the total tumor specimen and in at least two high-power fields)
  • Age greater than or equal to 18 years old and less than 75 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

  • A minimum of one measurable lesion defined as:

    • Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST), OR
    • Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s)
  • Absolute neutrophil count (ANC) >= 1 x 10^9 cells/L (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
  • Platelets >= 75 x 10^9/L (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
  • Hemoglobin >= 9.5 g/dL (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
  • Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal (ULN) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
  • Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
  • Creatinine < 2 mg/dL (or a glomerular filtration rate > 45) (determined within 30-60 days prior to enrollment; re-evaluated within 14 days of beginning conditioning chemotherapy)
  • Patients with melanoma must have progressed following >= 1 line of systemic therapy, including immune checkpoint inhibitor and a BRAF inhibitor in combination with MEK inhibitor for patients with BRAF V600-activating mutation and is not considered to have an alternate treatment option with curative intent
  • Must be willing and able to accept at least one leukapheresis procedure (This does not apply for patients receiving a second infusion of IL13R a2 CAR T cells as they will not undergo leukapheresis)
  • Must be willing and able to provide written informed consent

Exclusion Criteria:

  • Inability to purify >= 1 x 10^7 T cells from leukapheresis product (this does not apply to patients receiving a second infusion of IL13Ra2 CAR T cells as they will not undergo leukapheresis)
  • Previously known hypersensitivity to any of the agents used in this study; known sensitivity to cyclophosphamide or fludarabine
  • Received systemic treatment for cancer, including immunotherapy, within 14 days prior to initiation of conditioning chemotherapy administration within this protocol
  • Clinically active brain metastases. Radiological documentation of absence of active brain metastases at screening is required for all patients. Prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment
  • Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment; not including patients with primary or secondary adrenal insufficiency who require physiologic replacement with steroids, or patients on inhaled or topical steroids at standard doses
  • Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
  • Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
  • A Tiffeneau-Pinelli index < 70% of the predicted value. Subjects will be excluded if pulmonary function tests indicate they have insufficient pulmonary capability
  • Patients will be excluded if they have a history of clinically significant electrocardiography (ECG) abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress multigated acquisition scan (MUGA), dobutamine echocardiogram, or other stress test)
  • Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT (QTC) > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (HR > 120 beats per minute) will be evaluated by a cardiologist prior to starting the trial. Patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 ventricular premature complex [PVC]s per minute), ventricular tachycardia, 3rd degree heart block will be excluded from the study unless cleared by a cardiologist
  • Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and for 6 months afterwards. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) at screening and again within 14 days from starting the conditioning chemotherapy. The definition of effective contraception will be based on the judgment of the study investigators. Patients who are breastfeeding are not allowed on this study
  • A concomitant active malignancy that would be considered to interfere with the assessment of the primary or secondary endpoints of the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (chemotherapy, IL13Ralpha2)
Patients may receive cyclophosphamide IV over 60 minutes on days -5 to -3 and fludarabine phosphate IV over 15-30 minutes on days -5 to -2. Patients then receive IL13Ralpha2 CAR T cells IV on day 0. Patients also undergo biopsy at baseline and on study, CT, or PET and CT scan at screening and on study, magnetic resonance imaging (MRI) throughout the trial, and collection of blood samples throughout the trial. Patients with disease progression may receive a second cycle with an infusion of IL13Ralpha2 CAR T cells.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Drug: Cyclophosphamide
Given IV
Other Names:
  • Cytoxan
  • CTX
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamide Monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
  • Asta B 518
  • B-518
  • WR-138719
Procedure: Biopsy
Undergo biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Procedure: Positron Emission Tomography
Undergo PET scan
Other Names:
  • Medical Imaging, Positron Emission Tomography
  • PET
  • PET Scan
  • Positron Emission Tomography Scan
  • Positron-Emission Tomography
  • proton magnetic resonance spectroscopic imaging
  • PT
  • Positron emission tomography (procedure)
Procedure: Computed Tomography
Undergo CT scan
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • SH T 586
Biological: IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells
Given IV
Other Names:
  • IL13 [EQ]BBzeta/truncated CD19[t]+ Naive and Memory T Cells
  • IL13 [EQ]BBzeta/truncated CD19[t]+ TN/MEM Cells
  • IL13Ra2-specific-hinge-optimized-4-1BB-CAR/truncated CD19-expressing Autologous TN/MEM Lymphocytes
Other: Fludeoxyglucose F-18
Undergo FDG-PET/CT scan
Other Names:
  • 18FDG
  • FDG
  • fludeoxyglucose F 18
  • Fludeoxyglucose (18F)
  • Fludeoxyglucose F18
  • Fluorine-18 2-Fluoro-2-deoxy-D-Glucose
  • Fluorodeoxyglucose F18

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: Up to 90 days from the day of chimeric antigen receptor (CAR)-transgenic cell infusion
Safety will be reported as incidence rates for adverse events, serious adverse events, and fatal adverse events for Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 3 or higher. Adverse events will be tabulated by treatment group and will include the number of patients for whom the event occurred, the rate of occurrence, and the severity and relationship to study drug.
Up to 90 days from the day of chimeric antigen receptor (CAR)-transgenic cell infusion
Dose-limiting toxicity
Time Frame: Up to 28 days from the day of CAR-transgenic cell infusion
Up to 28 days from the day of CAR-transgenic cell infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: Up to 120 days
Will be recorded following the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Up to 120 days
Response for in-transit metastasis
Time Frame: Up to 2 years
Up to 2 years
Overall survival
Time Frame: From the date of CAR T cell infusion in the clinical trial until death, whether related to the trial or not, assessed up to 2 years
From the date of CAR T cell infusion in the clinical trial until death, whether related to the trial or not, assessed up to 2 years
IL13Ralpha2 CAR T cell persistence
Time Frame: At days 1, 7, 14, 30, 60, 90, and 120
At days 1, 7, 14, 30, 60, 90, and 120
IL13Ralpha2 CAR T Cell phenotypic monitoring
Time Frame: Up 2 years
Up 2 years
Complete response (CR)
Time Frame: At day 30, 60, 120, and every 2-3 months for up to 2 years
At day 30, 60, 120, and every 2-3 months for up to 2 years
Partial response (PR)
Time Frame: At day 60, 120, and every 2-3 months for up to 2 years
At day 60, 120, and every 2-3 months for up to 2 years
Progression-free survival
Time Frame: Time from study enrollment to the date of progressive disease first documented disease progression per RECIST v1.1 or death due to any cause by investigator assessment, whichever occurs first, assessed up to 2 years
Time from study enrollment to the date of progressive disease first documented disease progression per RECIST v1.1 or death due to any cause by investigator assessment, whichever occurs first, assessed up to 2 years
Time to disease progression
Time Frame: The length of time from the date of CAR T cell infusion to the date of progressive disease first documented, death, or the start of secondary antitumor therapy, assessed up to 2 years
The length of time from the date of CAR T cell infusion to the date of progressive disease first documented, death, or the start of secondary antitumor therapy, assessed up to 2 years
Duration of overall complete response
Time Frame: From the time measurement criteria is met for CR until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
From the time measurement criteria is met for CR until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
Duration of overall response
Time Frame: From the time measurement criteria is met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years
From the time measurement criteria is met for CR/PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of an endogenous T cell anti-tumor response
Time Frame: Up 2 years
The biopsies will be analyzed by hematoxylin and eosin staining (H&E), immunohistochemistry (IHC) to quantify the numbers of T lymphocytes. If sufficient quantity of tissue is available, the study investigators will attempt to monitor the phenotype of the TIL obtained from tumor biopsy samples by multicolor flow cytometry (FACS), and other immune monitoring assays.
Up 2 years
Cytokine release syndrome analysis
Time Frame: Up 2 years
Up 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Anusha Kalbasi

Collaborators

Jonsson Comprehensive Cancer Center
California Institute for Regenerative Medicine (CIRM)
City of Hope National Medical Center
Melanoma Research Alliance

Investigators

  • Principal Investigator: Antoni Ribas, MD, PhD, University of California, Los Angeles
  • Principal Investigator: Allison Betof Warner, MD, PhD, Stanford University
  • Principal Investigator: Yan Xing, MD, PhD, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 7, 2025

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

September 25, 2019

First Submitted That Met QC Criteria

October 4, 2019

First Posted (Actual)

October 8, 2019

Study Record Updates

Last Update Posted (Actual)

March 17, 2026

Last Update Submitted That Met QC Criteria

March 13, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-77842
  • NCI-2019-05764 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Biospecimen Collection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Macedonia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe