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| ID | Type | Description | Link |
|---|---|---|---|
| R01CA296807-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Bellicum Pharmaceuticals | INDUSTRY |
| National Cancer Institute (NCI) | NIH |
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The purpose of this study is to test the safety and tolerability of using a new treatment called autologous T lymphocyte chimeric antigen receptor cells against the CSPG4 antigen (iC9.CAR-CSPG4 T cells) in patients with head and neck cancer that came back after receiving standard therapy for this cancer. The iC9.CAR-CSPG4 treatment is experimental and has not been approved by the Food and Drug Administration.
How many (dose) of the iC9.CAR. CSPG4 T cells are safe to use in patients without causing too many side effects, and what is the maximum dose that could be tolerated will be investigated. The information collected from the study would help cancer patients in the future.
There are two parts to this study. In part 1, blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy.
The data from the dose escalation will be used to determine a recommended phase 2 dose (RP2D), which will be decided based on the maximum tolerated dose (MTD). Additionally, recommended phase 2 dose will be tested.
Eligible subjects will receive lymphodepletion chemotherapy standard followed by infusion of iC9-CAR.CSPG4 T cells. After treatment completion or discontinuation, subjects will be followed since involving gene transfer experiments.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Chimeric Antigen Receptors | Experimental | blood will be collected to prepare the iC9.CAR-CSPG4 T cells. Disease-fighting T cells will be isolated and modified to prepare the iC9.CAR-CSPG4 T cells. In part 2, the iC9.CAR-CSPG4 T cells are given by infusion after completion of lymphodepletion chemotherapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | cyclophosphamide 300 mg/meter square IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Toxicity: NCI-CTCAE | Toxicity will be graded as the Number of participants with adverse events (AE)s AEs will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Dose Limiting Toxicities (DLTs) is defined as at least possibly related to CAR.B7-H3T cell product administration. | Up to 4 weeks |
| Toxicity: Cytokine Release Syndrome (CRS) | CRS will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild: Fever ≥38^ o C, No hypotension, No hypoxia, Grade 2 - Moderate: Fever ≥38^ o C, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe: Fever ≥ 38^ o C, Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening: Fever ≥38^oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g. Continuous positive airway pressure, BiPAP, intubation, mechanical ventilation), Grade 5 - Death | Up to 4 weeks |
| Toxicity: Immune effector cell-associated neurotoxicity syndrome (ICANS) | Neurotoxicity will be graded according to the Immune effector cell-associated neurotoxicity syndrome (ICANS) criteria. Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death). | Up to 4 weeks |
| Dose Limiting Toxicity | An event will be considered a Dose limiting toxicity per NCI CTCAE version 5.0, the CRS Grading and ICANS grading criteria.
|
| Measure | Description | Time Frame |
|---|---|---|
| The recommended phase 2 dose (RP2D) of iC9-CAR.CSPG4 | The recommended phase 2 dose (RP2D) for administration of iC9-CAR.CSPG4 T cells will be determined based on the modified 3+3 dose finding rule and the tolerability of iC9-CAR.CSPG4 T cells. tolerability of iC9-CAR.CSPG4 T cells will be assessed by NCI-CTCAE v5, ASTCT Consensus ICANS Grading, and CRS Grading Criteria. | Up to 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) | PFS will be measured from the first day of lymphodepletion chemotherapy prior to iC9- CAR.CSPG4 T cell infusion to progression per RECIST 1.1 or death. | Up to 2 years |
| Overall Survival (OS) |
Inclusion Criteria:
Unless otherwise noted, subjects must meet all of the following criteria to participate in all phases of the study:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Catherine Cheng | Contact | +1 919-445-4208 | UNCImmunotherapy@med.unc.edu | |
| Spencer SB Laing | Contact | +1 919-445-4175 | UNCImmunotherapy@med.unc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Jared Weiss, MD | UNC Lineberger Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lineberger Comprehensive Cancer Center at University of North Carolina Chapel Hill | Recruiting | Chapel Hill | North Carolina | 27599 | United States |
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| Label | URL |
|---|---|
| University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials | View source |
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| ID | Term |
|---|---|
| D006258 | Head and Neck Neoplasms |
| D012008 | Recurrence |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D064987 | Cell- and Tissue-Based Therapy |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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| Fludarabine | Drug | fludarabine 30 mg/meter square IV × 3 days |
|
|
| Cell Therapy | Biological | the autologous T lymphocyte chimeric antigen receptor cells against the CSPG4 antigen iC9-CAR.CSPG4 T cell infusion iC9-CAR.CSPG4 T cell infusion |
|
| Up to 4 weeks |
| Objective response rate | The objective response rate will be assessed per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) and immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). RECIST v1.1: Complete Response (CR) as Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects. irRECIST: Complete Response (irCR), Disappearance of all lesions, no new lesions, lymph nodes < 10 mm in short axis; Partial Response (irPR), ≥30% decrease in the sum of target lesions and non-target lesions are irNN; Stable response (irSD), not meeting criteria for irCR, irPR, or irPD; Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir. | Up to 2 years |
OS will be measured from the first day of lymphodepleting chemotherapy prior to iC9-CAR.CSPG4 T cell infusion to date of death for any cause.
| Up to 2 years |
| Duration of Response (DOR) | DOR is defined as the time from partial response (PR) or better to progressive disease (PD) per RECIST 1.1. and irRECIST. | Up to 2 years |
| Feasibility of iC9-CAR.CSPG4 T cell therapy | Feasibility will be determined by measuring the percent of subjects procured that proceed with lymphodepletion followed by iC9-CAR.CSPG4 T cell infusion. | From cell procurement to 4 weeks after iC9-CAR.CSPG4 T cell infusion. |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |