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

Phase 1/Phase 2
18 Years
Open (Enrolling)

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Trial Information

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

Purpose of this study is to evaluate the safety and tolerability of autologous genetically
modified T cells. Genetic material is transferred into the subject's previously harvested
autologous T cells to redirect them to target melanoma cells rather than their usual target.
Study subjects must have histologically or cytologically melanoma stage 3/4 and their tumor
must express HLA Class 1 allele HLA-A*0201 for NY-ESO-1/LAGE. Subjects must also have
measureable disease on study entry, as defined by at least one lesion that can be measured
in at least one dimension >= 10mm with spiral CT scan.

Inclusion Criteria:

- 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

- Age ≥ 18 years.

- 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 ≥ 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

- Tumor must express the cancer-testis antigen as determined by the study laboratory.
The patient must express the appropriate HLA class I allele (HLA-A2 for NY-ESO-1).

- The effects of transduced T cells on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason and because cyclophosphamide is known
to be teratogenic, women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence)
prior to study entry and for the duration of study participation. Should a woman
become pregnant or suspect she is pregnant while participating in this study, she
should inform her treating physician immediately.

- Ability of the patient (or legally authorized representative if applicable) to
understand and the willingness to sign a written informed consent document.

- Both men and women and members of all races and ethnic groups are all eligible

Exclusion Criteria:

- 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

- 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. PI will use his or her discretion to choose the stress test best
suited to evaluate the patient.

- Pregnant women are excluded from this study because cyclophosphamide has the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with cyclophosphamide, breastfeeding should be discontinued if the mother is
treated with cyclophosphamide. These potential risks may also apply to other agents
used in this study.

- Active infection with HIV, HPV or HCV as defined by positive serology for HIV,
Hepatitis B, or Hepatitis C. Patients are excluded due to the immunosuppressive dose
of cyclophosphamide used and the unknown risks associated with viral replication.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and Tolerability

Outcome Description:

To determine the safety and tolerability of a fixed split-dose of autologous t cells transduced with lentiviral vector encoding an enhanced TCR after non-myeloablative chemotherapy.

Outcome Time Frame:

Daily monitoring from Day1-Day 16, weekly therafter through week 12, monthly therafter through month 12.

Safety Issue:


Principal Investigator

Gerald P Linette, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University in St. Louis


United States: Food and Drug Administration

Study ID:

UPCC 01611



Start Date:

May 2011

Completion Date:

February 2030

Related Keywords:

  • Melanoma
  • Melanoma
  • Melanoma



Washington University in St. Louis St. Louis, Missouri  63110
Yale School of Medicine New Haven, Connecticut  06510