Phase I/II Study to Assess the Safety and Activity of Enhanced TCR Transduced Autologous T Cells in Metastatic Melanoma

NCT01350401 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: ADP 01611
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this early (phase I/II) clinical trial is to assess the effects (both good and bad) of genetically modified T cells after chemotherapy on your cancer and general health.

Conditions

Melanoma

Keywords

Melanoma; Cell Therapy; T Cell Therapy; NY-ESO-1; Immuno-oncology; Metastatic; Previously treated; T Cell Receptor

Outcome Measures

Primary Outcomes (1)

• Adverse Events Related to Study Treatment

  Number of Participants with NCI CTC V.4 Adverse Events related to study treatment greater than or equal to Grade 3

  Up to 12 months

Secondary Outcomes (3)

• Tumor Response

  Change from Baseline, every 4 weeks until Month 5 and then every other month through Month 11

• Determine the Functional Properties and Phenotype of Modified T-cells From Peripheral Blood and Tumor Sites.

  8 Weeks post T-cell infusion

• Peak Persistence of Modified T-cells in the Peripheral Blood

  Days 1, 5-9, 12-16, weekly thereafter through Week 12, monthly thereafter through Month 12, and during LTFU

Study Arms (1)

NY-ESO-1/LAGE-1 and HLA-A*02 Positive Subjects

EXPERIMENTAL

Genetic: Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T

Interventions

Autologous genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T GENETIC

Cytoreductive chemotherapy followed by infusion of NY-ESO-1ᶜ²⁵⁹T

NY-ESO-1/LAGE-1 and HLA-A*02 Positive Subjects

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 histologically or cytologically confirmed melanoma stage III/IV, unresectable
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with spiral CT scan
• One prior cytotoxic therapy for the treatment of metastatic disease is allowed. Unlimited regimens using biological agents (vaccines), immunotherapy, or targeted agents is permitted. For example, BRAF inhibitors and ipilimumab are permitted. Patients must have fully recovered from the acute toxicities related to any prior therapy. Prior therapy must be completed ≥28 days before the first dose of cyclophosphamide.
• Age ≥18
• Life expectancy of greater than 3 months
• ECOG performance status ≤ 1
• Patients must have normal organ and marrow function as defined below:
• Leukocytes ≥ 3,000/mcL
• Absolute Neutrophil Count (ANC) ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal
• Creatinine ≤ 2.0 mg/dl Or Creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• The patient must express HLA class I allele HLA-A\*0201 for NY-ESO-1/LAGE.
• Patient must have proven positive tumor sample for NY-ESO-1 as determined by an H score for immunohistochemistry staining. Positive expression is defined as an H score ≥ 100 where the H score = \[2 x (% cells 2+) + 3 x (% cells 3+)\].

You may not qualify if:

• Patients who have had 2 or more regimens containing cytotoxic chemotherapy for metastatic melanoma.
• Patients may not be receiving any other investigational agents.
• Patients with active brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide or other agents used in the study.
• Active infection
• Prior malignancy (except non-melanoma skin cancer) within 3 years.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. All patients will undergo a cardiac stress test for evaluation of cardiac function.
• Pregnant or nursing females
• Active infection with HIV, HBV or HCV as defined below, due to the immunosuppressive effects of cyclophosphamide used and the unknown risks associated with viral replication.
• Positive serology for HIV
• Active Hepatitis B infection as determined by test for hepatitis B surface antigen.
• Active Hepatitis C. Patients will be screened for HCV antibody. If the HCV antibody is positive, a screening HCV RNA by any RT-PCR or bDNA assay must be performed at screening by a local laboratory with a CLIA certification or its equivalent. Eligibility will be determined based on a negative screening value. The test is not required if documentation of a negative result of a HCV RNA test performed within 60 days prior to screening is provided.

Sponsors & Collaborators

• Adaptimmune: lead

Study Sites (2)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Trials Management
• Organization: Adaptimmune

clinicaltrials@adaptimmune.com

Study Officials

• Gerald P Linette, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

• Harriet Kluger, MD

  Yale New Haven Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: May 9, 2011
• Study Start: June 1, 2011
• Primary Completion: February 17, 2016
• Study Completion: March 1, 2018
• Last Updated: January 10, 2019
• Results First Posted: May 8, 2018

Record last verified: 2019-01

Locations

US (2)