RecruitingPhase 1

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 75 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 2 years, 3 years
  • Procedures mentioned: Blood draws, MRI scans, CT scans, Biopsies, Infusions

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "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."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests the safety and best dose of gene-changed immune cells called IL13Ralpha2 CAR T cells, given after chemotherapy. The cells come from the patient's own blood and are changed to target cancer. It is for adults ages 18–74 with stage IIIC or IV melanoma, a skin cancer, or other solid tumors that have spread.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 18–74 and able to do most daily tasks with little or no help.
  • Have cancer confirmed by a tissue test that surgery cannot cure: stage IIIC or IV melanoma, or another solid tumor that has spread and did not start in the brain or spinal cord.
  • Your tumor must have enough of a protein called IL13Ralpha2, based on a lab test.
  • For melanoma, cancer must have worsened after at least one drug treatment, including immune therapy and, for certain BRAF gene changes, BRAF and MEK drugs. No other treatment aimed at a cure can be available.
  • For other solid tumors, cancer must have returned or resisted all standard whole-body drug treatments you can receive.
  • Have at least one tumor that can be measured, and blood counts, liver tests, and kidney tests that meet study limits.
  • Be willing and able to have blood collected to separate out immune cells. This is not needed for a second infusion.
  • Be willing and able to sign a form agreeing to join the study.

Who can't join

  • Too few T cells can be collected for treatment, or you have a known allergy to a study drug. The cell collection rule does not apply to a second infusion.
  • You received whole-body cancer treatment, including immune therapy, within 14 days before study chemotherapy.
  • Cancer in the brain is active. Previously treated brain tumors may be allowed if they are under control.
  • You may need steroids that affect the whole body or other immune-suppressing drugs, or used whole-body steroids within 2 weeks before joining. Some hormone-replacement, inhaled, and skin steroids are allowed.
  • You have HIV or another condition that weakens the immune system, or hepatitis B or C with ongoing liver damage.
  • You have dementia or major changes in thinking that prevent consent or following study rules, or another active cancer that could affect study results.
  • Lung tests show poor breathing ability, or heart tests show certain serious problems. Some heart rhythm problems require clearance from a heart doctor.
  • You are pregnant or breastfeeding. Women who could become pregnant must have negative pregnancy tests and agree to effective birth control during treatment and for 6 months afterward.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

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 sites (3)

CA