Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma

Summary

Objectives:

The primary objective will be to determine whether patients receiving the combination of dendritic cells and high dose IL-2 (Cohort A) have sustained persistence of infused T cells compared to patients treated with T cells and high dose IL-2 alone.

Secondary endpoints will include evaluations for tumor response and studies to determine whether dendritic cells enhance the infused T cells in anti-tumor activity and their ability to migrate to the tumor site. In addition, we will evaluate the characteristics of the infused T cells that correspond with effectiveness in vivo.

Additionally, secondary objectives will include correlation of clinical parameters with survival (overall survival and progression-free survival) for all cohorts.

COHORT C

In a separate cohort (Cohort C) the primary endpoint will be the overall response rate of TIL treatment for patients who have not achieved PR or CR or have progressive disease from treatment of the BRAF inhibitor alone.

COHORT D

The primary objective of Cohort D is to confirm the safety of adoptively transferred, TIL into the CSF.

The secondary objective is the evaluation of clinical imaging and CSF response. Correlative objectives will assess if the intrathecally-infused T cells persist in the CSF, assess circulating tumor cells in the CSF, and assess various cytokine and other analyses,as feasible.

COHORT E

The primary objective of Cohort E is to determine the overall response rate of TIL treatment with cells grown by the TIL 3.0 pre-REP (Turnstile 1) phase of cellular growth.

Conditions

• Melanoma

Interventions

BIOLOGICAL

Intrathecal Interleukin-2

1.2 MIU of IL- 2 on Day 2, 4, 9, 11, 16 and 18 as tolerated. Then, patient receives twice weekly IL-2 that will be gradually changed to weekly IL-2. After 4-6 weeks patients switched to IL-2 maintenance.

BIOLOGICAL

Dendritic Cell Immunization

1x10\^7 to 2.5x10\^8 MART-1 peptide-pulsed Dendritic Cells given by vein over 20-30 minutes approximately 4 hrs after receiving T cells.

DRUG

Cyclophosphamide

60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion

DRUG

Fludarabine

25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.

BIOLOGICAL

T-Cells

On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.

BIOLOGICAL

Interleukin-2

12-16 hours after completing the T cell infusion, all will receive high dose IL-2 on an inpatient basis at the standard dose of 720,000 IU/kg as an intravenous bolus over approximately a 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26 (+/- 7 days), as tolerated.

DRUG

Mesna

60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.

BIOLOGICAL

Intrathecal T-Cells

5.0x10\^9 T-cells administered on Day 1, and 10x10\^9 T-cells on Day 15. 1.2 MIU of IL- 2 on Day 2, 4, 9, 11, 16 and 18 as tolerated.

Sponsors & Collaborators

• Prometheus Laboratories

  collaborator INDUSTRY

• Key Biologics, LLC

  collaborator INDUSTRY

• National Cancer Institute (NCI)

  collaborator NIH

• Adelson Medical Research

  collaborator UNKNOWN

• M.D. Anderson Cancer Center

  lead OTHER

Principal Investigators

• Rodabe N. Amaria, MD · M.D. Anderson Cancer Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2006-02-01

Primary Completion

2030-02-28

Completion

2030-02-28

FDA Drug

Yes

Countries

• United States

Study Locations