Clinical Trials /

Transfer of Genetically Engineered Lymphocytes in Melanoma Patients

NCT01586403

Description:

This is a phase one trial to determine if genetically engineered lymphocytes can be safely delivered to patients with metastatic melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Transfer of Genetically Engineered Lymphocytes in Melanoma Patients
  • Official Title: Transfer of Genetically Engineered Lymphocytes in Melanoma Patients: A Phase 1 Dose Escalation Study

Clinical Trial IDs

  • ORG STUDY ID: 203732
  • SECONDARY ID: R44CA126461
  • SECONDARY ID: P01CA154778
  • NCT ID: NCT01586403

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
Dose 1Dose 1
Dose 2Dose 2
Dose 3Dose 3
Dose 4Dose 4

Purpose

This is a phase one trial to determine if genetically engineered lymphocytes can be safely delivered to patients with metastatic melanoma.

Detailed Description

      The goal of this study is to establish the recommended phase two dose of autologous T cell
      receptor transduced T cells when administered with low dose IL-2 to stage IV melanoma
      patients following a non-myeloablative and lymphodepleting chemotherapy preparative regimen.
      A secondary objective is to evaluate biologic and immunologic parameters associated with the
      adoptively transferred T cell receptor transduced T cells, including auditory and visual
      changes. The investigators believe the infusion of T cell receptor gene modified autologous T
      cells can mediate objective clinical responses in stage IV melanoma patients.
    

Trial Arms

NameTypeDescriptionInterventions
Dose 1ExperimentalSubjects in cohort 1 will receive 2.5 x 106 TIL 1383I TCR transduced T cells per kg body weight
  • Dose 1
Dose 2Experimentalcohort 2 will receive 7.5 x 106 TIL 1383I TCR transduced T cells per kg body weight.
  • Dose 2
Dose 3ExperimentalSubjects in cohort 3 will receive 2.5 x 107 TIL 1383I TCR transduced T cells per kg body weight.
  • Dose 3
Dose 4ExperimentalSubjects will then receive a single infusion of autologous bulk TIL 1383I TCR transduced T cells supported with low dose IL-2. Autologous bulk TIL 1383I TCR transduced T cells means the infusion will consist of a polyclonal mixture of CD4+ and CD8+ T cells expressing the TIL 1383I TCR. Subjects in cohort 4 will receive 7.5 x 107 TIL 1383I TCR transduced T cells per kg body weight.
  • Dose 4

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have a diagnosis of metastatic melanoma which is measurable 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 of 0 or 1 ECOG PS scale (see Appendix B).

          -  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 per Loyola
             University Medical Center pathologic review from FNA/core/excisional biopsy of lesion.

          -  Cardiac ejection fraction >50% as determined by screening echocardiogram.

          -  Patients that have undergone treatment with anti-CTLA-4 (Cytotoxic T-Lymphocyte
             Antigen 4) antibody must have at least 3 months from last dose of CTLA-4 antibody
             before they can be enrolled into this study.

          -  The patients BRAF mutation status at position 600 must be known prior to enrollment.
             Patients with V600E mutations are eligible if they have failed Vemurafenib therapy or
             have been offered Vemurafenib therapy and refused.

          -  Patients treated with prior Interleukin-2 will be allowed to be in this study.

        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 six 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/men of reproductive potential must have
             agreed to use an effective contraceptive method.

          -  Patients whose BRAF V600E mutation status is unknown, have the BRAF V600E mutation and
             are responding to Vemurafenib therapy, or have the BRAF V600E mutation and have not
             been offered the option of receiving Vemurafenib therapy for the treatment of their
             melanoma.

          -  No other 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 five years.

          -  Patients that have undergone Tyrosinase immunotherapy.

          -  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 109/L

               -  Platelet count less than 100 x 109/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 (e.g., 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:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Find dose of autologous T cell receptor
Time Frame:4 weeks
Safety Issue:
Description:Establish the recommended phase two dose of autologous T cell receptor transduced T cells when administered with low dose IL-2 to stage IV melanoma patients

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Loyola University

Trial Keywords

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

Last Updated