Health TrialsbyHealthPanel

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

ConditionsMetastatic Malignant Solid NeoplasmMetastatic MelanomaPathologic Stage IIIC Cutaneous Melanoma AJCC v8Pathologic Stage IV Cutaneous Melanoma AJCC v8Recurrent Malignant Solid NeoplasmRefractory Malignant Solid NeoplasmUveal MelanomaAcral MelanomaNeuroendocrine TumorsParagangliomaPheochromocytomaAdrenocortical CarcinomaPancreatic Neuroendocrine TumorThyroid CancerBreast CancerLung AdenocarcinomaHead and Neck Squamous Cell Carcinoma
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorAnusha Kalbasi

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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)

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • Biopsy

    Procedure/Surgery

    Undergo biopsy

  • Biospecimen Collection

    Procedure/Surgery

    Undergo collection of blood samples

  • Computed Tomography

    Procedure/Surgery

    Undergo CT scan

  • Cyclophosphamide

    Drug

    Given IV

  • Fludarabine Phosphate

    Drug

    Given IV

  • Fludeoxyglucose F-18

    Other intervention

    Undergo FDG-PET/CT scan

  • IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells

    Biological/Vaccine

    Given IV

  • Magnetic Resonance Imaging

    Procedure/Surgery

    Undergo MRI

  • Positron Emission Tomography

    Procedure/Surgery

    Undergo PET scan

Treatment groups

18 Participants
are divided into 1 treatment group
Group A: Treatment (chemotherapy, IL13Ralpha2)Experimental treatment 9 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
Up to 90 days from the day of chimeric antigen receptor (CAR)-transgenic cell infusion
2

Dose-limiting toxicity

Time frame
Up to 28 days from the day of CAR-transgenic cell infusion

Secondary outcomes

1

Objective response rate

Will be recorded following the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

Time frame
Up to 120 days
2

Complete response (CR)

Time frame
At day 30, 60, 120, and every 2-3 months for up to 2 years
3

Partial response (PR)

Time frame
At day 60, 120, and every 2-3 months for up to 2 years
4

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

Other outcomes

1

Cytokine release syndrome analysis

Time frame
Up 2 years
2

Evaluation of an endogenous T cell anti-tumor response

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.

Time frame
Up 2 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Anusha Kalbasi

Lead sponsor

Stanford University

Sponsor institution

Melanoma Research Alliance

Collaborator

California Institute for Regenerative Medicine (CIRM)

Collaborator

City of Hope National Medical Center

Collaborator

Jonsson Comprehensive Cancer Center

Collaborator

Source ClinicalTrials.gov
Apply now