Gene Modified Immune Cells After Conditioning Regimen for the Treatment of Stage IIIC or IV Melanoma or Metastatic Solid Tumors
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
2 other identifiers
interventional
18
1 country
3
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2025
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 25, 2019
CompletedFirst Posted
Study publicly available on registry
October 8, 2019
CompletedStudy Start
First participant enrolled
October 7, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2026
March 17, 2026
March 1, 2026
12 months
September 25, 2019
March 13, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events
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
Up to 28 days from the day of CAR-transgenic cell infusion
Secondary Outcomes (11)
Objective response rate
Up to 120 days
Complete response (CR)
At day 30, 60, 120, and every 2-3 months for up to 2 years
Partial response (PR)
At day 60, 120, and every 2-3 months for up to 2 years
Progression-free survival
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
Response for in-transit metastasis
Up to 2 years
- +6 more secondary outcomes
Other Outcomes (2)
Cytokine release syndrome analysis
Up 2 years
Evaluation of an endogenous T cell anti-tumor response
Up 2 years
Study Arms (1)
Treatment (chemotherapy, IL13Ralpha2)
EXPERIMENTALPatients 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.
Interventions
Undergo CT scan
Given IV
Given IV
Undergo FDG-PET/CT scan
Undergo MRI
Undergo PET scan
Undergo collection of blood samples
Given IV
Eligibility Criteria
You may qualify if:
- 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)
- +4 more criteria
You may not qualify if:
- 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
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Melanoma Research Alliancecollaborator
- City of Hope National Medical Centercollaborator
- Jonsson Comprehensive Cancer Centercollaborator
- Anusha Kalbasilead
- California Institute for Regenerative Medicine (CIRM)collaborator
Study Sites (3)
City of Hope
Duarte, California, 91010, United States
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095, United States
Stanford Cancer Institute
Stanford, California, 93405, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Allison Betof Warner, MD, PhD
Stanford University
- PRINCIPAL INVESTIGATOR
Antoni Ribas, MD, PhD
University of California, Los Angeles
- PRINCIPAL INVESTIGATOR
Yan Xing, MD, PhD
City of Hope Medical Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
September 25, 2019
First Posted
October 8, 2019
Study Start
October 7, 2025
Primary Completion (Estimated)
October 1, 2026
Study Completion (Estimated)
October 1, 2026
Last Updated
March 17, 2026
Record last verified: 2026-03