Transfer of Genetically Engineered Lymphocytes in Melanoma Patients

NCT01586403 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: 203732R44CA126461P01CA154778
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Melanoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Find dose of autologous T cell receptor

  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

  4 weeks

Study Arms (4)

Dose 1

EXPERIMENTAL

Subjects in cohort 1 will receive 2.5 x 106 TIL 1383I TCR transduced T cells per kg body weight

Biological: Dose 1

Dose 2

EXPERIMENTAL

cohort 2 will receive 7.5 x 106 TIL 1383I TCR transduced T cells per kg body weight.

Biological: Dose 2

Dose 3

EXPERIMENTAL

Subjects in cohort 3 will receive 2.5 x 107 TIL 1383I TCR transduced T cells per kg body weight.

Biological: Dose 3

Dose 4

EXPERIMENTAL

Subjects 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.

Biological: Dose 4

Interventions

Dose 1 BIOLOGICAL

Subjects will 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. cohort 1 will receive 2.5 x 106 TIL 1383I TCR transduced T cells per kg body weight. Subject in cohort 1 will receive 2.5 x 10\^6 TIL 1383I TCR transduced T cells per kg body weight.

Dose 1

Dose 2 BIOLOGICAL

Subjects will 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 2 will receive 7.5 x 10\^6 TIL 1383I TCR transduced T cells per kg body weight.

Dose 2

Dose 3 BIOLOGICAL

Subjects will 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 3 will receive 2.5 x 10\^7 TIL 1383I TCR transduced T cells per kg body weight.

Dose 3

Dose 4 BIOLOGICAL

Subjects 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 10\^7 TIL 1383I TCR transduced T cells per kg body weight.

Dose 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Loyola University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michael Nishimura, PhD

  Loyola University Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: April 26, 2012
• Study Start: July 1, 2012
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: October 30, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)