Study With T-cel Receptor Gene Therapy in Metastatic Melanoma

NCT02654821 | Unknown Phase 1 DMC

• 1 other identifier: M11TCR
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with stage IV melanoma (also eye melanoma) will be treated with TCR transduced cells.

Conditions

Stage IV Skin Melanoma; Eye; Melanoma

Keywords

Melanoma; TCR

Outcome Measures

Primary Outcomes (2)

• Safety of the TCR treatment (according to CTCAE 4.0)

  Safety of the TCR treatment will be measured by noting the toxicity (according to CTCAE 4.0) that the patient experiences while on treatment.

  Baseline until release from the hospital, about 4 weeks.

• Objective response rate according to RECIST 1.1.

  The objective response rate will be measured by RECIST 1.1.

  Baseline until progressive disease, median 6 months.

Secondary Outcomes (4)

• 1-year progression free survival (PFS)

  Baseline until 1 year after treatment.

• Efficacy of induction of tumor specific T cell responses as measured by the persistence of Melan-A/MART1 specific T cells in peripheral blood samples

  Baseline until progressive disease, median 6 months.

• Overall survival

  Assessed up to 12 months

• Systemic release of inflammatory cytokines after administration of transduced T cells compared to baseline

  Baseline until progressive disease, median 6 months.

Study Arms (1)

TCR treatment

EXPERIMENTAL

Eligible patients will undergo leukapheresis to isolate autologous T cells. These T cells will be transduced with a retroviral vector encoding the 1D3 HM CysTCR, and subsequently expanded during short-term ex vivo culture. Following pre-treatment with nonmyeloablative chemotherapy, patients will receive the adoptive transfer of autologous, TCR transduced T cells.

Biological: TCR transduced T-cells; Procedure: Biopsy; Procedure: Blood taking

Interventions

TCR transduced T-cells BIOLOGICAL

Eligible patients will undergo leukapheresis to isolate autologous T cells. These T cells will be transduced with a retroviral vector encoding the 1D3 HM CysTCR, and subsequently expanded during short-term ex vivo culture. Following pre-treatment with nonmyeloablative chemotherapy, patients will receive the adoptive transfer of autologous, TCR transduced T cells.

TCR treatment

Biopsy PROCEDURE

During screening, after treatment and at time of regression/progression a biopsy will be taken for translational research.

TCR treatment

Blood taking PROCEDURE

During screening, after the infusion with T-cells, after treatment and at time of regression/progression blood will be taken for translational research.

TCR treatment

Eligibility Criteria

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

You may qualify if:

• Patients must be ≥ 18 years of age.
• Patients must have inoperable stage IIIc or stage IV melanoma (AJCC), including ocular or mucosal melanoma, progressing after standard of care therapy, if available.
• Patients must be HLA-A\*0201 positive.
• The primary tumor and/or metastasis have to be positive for MART-1 (\>10% of tumor cells).
• Patients with measurable disease (RECIST 1.1)
• Patients must have a clinical performance status of ECOG 0 or 1.
• Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen.
• Patients must be able to understand and sign the Informed Consent document. Specific lab values

You may not qualify if:

• Life expectancy of less than three months.
• Requirement for systemic steroid therapy.
• Patients who have a history of CNS metastases.
• Patients with malignant pleural effusion or ascites.
• Any immunosuppressive chemotherapy or systemic steroid therapy within the last 3 weeks.
• Patients who have: history of coronary revascularization, documented LVEF of less than 45%, clinically significant atrial and/or ventricular arrhythmias including but not limited to atrial fibrillation, ventricular tachycardia, 2° or 3° heart block, documented FEV1 less than or equal to 60% predicted for patients with a history of cigarette smoking (greater than 20 pack/year within the past 2 years) and with symptoms of respiratory distress
• All patients' toxicities due to prior non-systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or focal palliative radiotherapy (to non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less.
• Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune disease requiring anti-TNF treatment.

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead

Study Sites (1)

Antoni van Leeuwenhoek ziekenhuis

Amsterdam, North Holland, 1066CX, Netherlands

Location

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

Biopsy

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; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• John B.A.G. Haanen, Prof.

  Antoni van Leeuwenhoek Ziekenhuis

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 13, 2016
• Study Start: March 1, 2012
• Primary Completion: October 1, 2019
• Study Completion: January 1, 2020
• Last Updated: November 2, 2018

Record last verified: 2018-10

Locations

NL (1)