Clinical Trials /

Adoptive T Cell Immunotherapy for Advanced Melanoma Using Engineered Lymphocytes

NCT02870244

Description:

Phase I clinical trial to determine the Phase II dose of autologous TIL 1383I TCR gene modified T Cells using a retrovirus. This is a novel National Cancer Institute (NCI) funded investigator initiated therapy for patients with advanced melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Adoptive T Cell Immunotherapy for Advanced Melanoma Using Engineered Lymphocytes
  • Official Title: Adoptive T Cell Immunotherapy for Advanced Melanoma Using Engineered Lymphocytes: A Phase 1b Study

Clinical Trial IDs

  • ORG STUDY ID: 203729
  • NCT ID: NCT02870244

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
Escalating DosesEscalating Doses

Purpose

Phase I clinical trial to determine the Phase II dose of autologous TIL 1383I TCR gene modified T Cells using a retrovirus. This is a novel National Cancer Institute (NCI) funded investigator initiated therapy for patients with advanced melanoma.

Detailed Description

      This is a Phase 1 dose escalation study designed to find the highest dose of TIL 1383I TCR
      transduced T cells that can safely be given. Three cohorts of 3 patients will be treated with
      increasing doses of TIL 1383I TCR transduced T cells. Patients will be monitored clinically
      and immunologically for a year after infusion. Subjects in Cohort 1 will receive 7.5 X
      10^6/kg TIL 1383I TCR transduced T cells. Subjects in Cohort 2 will receive 2.5 x 10^7/kg TIL
      1383I TCR transduced T cells. Subjects in Cohort 3 will receive 7.5 x 10^7/kg TIL 1383I TCR
      transduced T cells.
    

Trial Arms

NameTypeDescriptionInterventions
Escalating DosesExperimentalThree patients will be treated at the first & each subsequent dose level. Patients will be observed for 30 days post T cell infusion. If there was one DLT in the first 3 patients, an additional 3 patients will be treated at that level. If no additional DLTs are observed (for a total of 1 DLT in 6 patients) then the dose will be escalated. If two patients in the first 3 patients at a dose level experience a DLT, the dose will be de-escalated to the previous level & an additional 3 patients will be enrolled at that level if 6 have not yet been treated at that level. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 or 1 patient in six has experienced a DLT. If 2 or 3 patients in the first 3 patients experience a DLT at the first dose level, the study will terminate.
  • Escalating Doses

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a diagnosis of metastatic melanoma which is evaluable either
             clinically or radiologically.

          -  Patients must be 18 years of age or older.

          -  Patients must consent to be in the study and must have signed and dated an approved
             consent form, which conforms to federal and institutional guidelines.

          -  Patients must have a performance status (PS) of 0 or 1 ECOG PS scale.

          -  Patients must have the ability to provide written informed consent prior to study
             specific screening procedures, with the understanding that the patient has the right
             to withdraw from the study at any time.

          -  Patients melanoma must be positive for both tyrosinase and HLA-A2 pathologic review
             from FNA, core or excisional biopsy of lesion.

          -  Cardiac ejection fraction greater than 50 percent as determined by screening
             echocardiogram.

          -  Patients that have undergone treatment with anti-CTLA-4, Cytotoxic T-Lymphocyte
             Antigen 4, antibody must have at least 6 weeks from last dose of CTLA-4 antibody and
             evidence of tumor progression before they can be enrolled into this study.

          -  Patients that have undergone treatment with anti-PD-1, Programmed Death Receptor 1,
             Blockade or anti-PD-L1 antibody must have at least 4 weeks from last dose of antibody
             and evidence of tumor progression before they can be treated in this study.

          -  Patients with V600E mutations are eligible if they have failed an approved BRAF
             inhibitor or MEK inhibitor therapy or have refused treatment with an approved BRAF
             inhibitor or MEK inhibitor.

          -  Patients treated with prior Interleukin-2 (IL-2) are eligible.

          -  Sufficient cardiopulmonary reserve for IL-2 per institutional guidelines.

        Exclusion Criteria:

          -  Special classes of subjects such as fetuses, pregnant women, children, prisoners,
             institutionalized individuals, or others who are likely to be vulnerable.

          -  ECOG performance status of 2 or greater.

          -  Patients with a history metastatic melanoma involving the brain will be excluded if
             they have active disease or have had active disease within the prior three months that
             was not controlled with surgery or radiotherapy.

          -  Patients taking steroids for disease control or pain management

          -  Patients must not be pregnant or nursing because of the potentially harmful effects of
             these agents on a developing fetus. Women or men of reproductive potential must have
             agreed to use an effective contraceptive method.

          -  Patients whose BRAF V600 mutation status is unknown should undergo an attempt to
             determine this information, patients who have a BRAF V600 mutation and are responding
             to BRAF with or without MEK inhibitor therapy, or have a BRAF V600 mutation and have
             not been offered the option of receiving BRAF with or without MEK inhibitor therapy
             for the treatment of their melanoma are excluded.

          -  No prior malignancy is allowed except for the following- adequately treated basal cell
             or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or
             II cancer from which the patient is currently in complete remission, or any other
             cancer from which the patient has been disease-free for two years.

          -  Patients that have undergone immunotherapy targeting tyrosinase.

          -  Patients that have undergone immunotherapy in combination with non-myeloablative
             chemotherapy.

          -  Any of the following abnormal laboratory values Absolute neutrophil count less than
             1.5 x 10^9/L Platelet count less than 100 x 10^9/L Serum bilirubin greater than 1.5 x
             upper limit of normal ULN Serum ALT, AST greater than 2.5 x ULN Serum ALP greater than
             2 x ULN Serum Albumin less than 2.5 g dL International Normalized Ratio, INR greater
             than 1.5 Serum creatinine calculated creatinine clearance by the method of Cockcroft
             and Gault, less than 50mL min.

          -  Patients should not have any evidence of active or uncontrolled infection requiring
             treatment with antibiotics.

          -  Any severe or poorly controlled systemic disease, for example hypertension, clinically
             significant cardiovascular, pulmonary, or metabolic disease, disorders of
             wound-healing, ulcer or bone fracture.

          -  Patients who have received any chemotherapy or investigational treatment within 4
             weeks of study start.

          -  Known infection with HIV, HBV, or HCV.

          -  Known hypersensitivity to any of the components of the study drugs.

          -  Patients assessed by the investigator to be unable or unwilling to comply with the
             requirements of the protocol.
      
Maximum Eligible Age:89 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Approximately 18 patients with Grade 2 through Grade 5 Adverse Events that are related to study drug, graded according to NCI CTCAE Version 4.0
Time Frame:4 weeks
Safety Issue:
Description:Establish a recommended phase II dose of autologous T cell receptor transduced T cells by evaluating unexpected Grade 2 adverse events through Grade 5 regardless of attribution, all toxicities attributed to the cells, and all incidences of intubation including the duration and reason for intubation.

Secondary Outcome Measures

Measure:Immunologic changes in T cell count
Time Frame:Baseline and 4 weeks
Safety Issue:
Description:Change in T cell count from baseline to 4 weeks.
Measure:Audiologic changes of Grade 2 or higher as related to study drug, graded according to NCI CTCAE Version 4.0
Time Frame:Baseline and 4 weeks
Safety Issue:
Description:Potential auditory changes from baseline to 4 weeks.
Measure:Ophthalmologic changes or development of Uveitis of Grade 2 or higher as related to study drug, graded according to NCI CTCAE Version 4.0
Time Frame:Baseline and 4 weeks
Safety Issue:
Description:Potential visual changes from baseline to 4 weeks.
Measure:CT scans or physical examination from approximately 18 patients will be used to evaluate for a clinical objective response using RECIST Guideline Version 1.1
Time Frame:Baseline and 4 weeks
Safety Issue:
Description:CT scan or physical examination will be used to evaluate for a clinical objective response in patients who have received transduced T Cells at scheduled time points.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loyola University

Trial Keywords

  • Melanoma
  • Gene Therapy
  • Adoptive T-Cell Transfer
  • IL-2

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