Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma
3 other identifiers
interventional
1,230
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2006
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2006
CompletedFirst Submitted
Initial submission to the registry
February 10, 2006
CompletedFirst Posted
Study publicly available on registry
June 20, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 28, 2030
March 20, 2026
March 1, 2026
24.1 years
February 10, 2006
March 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Objective Response (OR)
Objective response (OR) defined as immune-related Best Overall Response (irBOR). irBOR is best confirmed immune-related response criteria (irRC) overall response over the study as a whole, recorded between the date of first dose until the last tumor assessment before subsequent therapy (except for local palliative radiotherapy for painful bone lesions) for the individual subjects in the study.
Clinical Evaluation during first 70 Days, CT Scan at 6-8 weeks (+/- 7 days) after cell infusion.
Longitudinal Immune Response in Cohort D
Longitudinal immune response defined as: Conversion of positive to negative cytology. Any perceptible improvement of the MRI findings confirmed by radiologist and/or the investigator confirmed by 2 successive MRIs 4 weeks apart. Any clinical improvement in terms of neurological symptoms.
4 weeks
Overall response rate (ORR) of TIL generated with the TIL 3.0 pre-REP methodology in Cohort E
ORR defined as CR/PR/SD\>6m (i.e., success = CR or PR or SD \> 6m).
At about 6 weeks and at 12 weeks after the T-cell and/or vaccine infusion
Study Arms (5)
Group A: Chemotherapy + IL-2 plus T-cells
EXPERIMENTALCyclophosphamide 60 mg/kg/d by vein (IV) over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m\^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10\^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26. Group A has been closed to new patient entry as of January 14, 2016.
Group B: Chemotherapy + IL-2 plus T-Cells + Vaccine
EXPERIMENTALChemotherapy and IL-2 plus T-cells and the vaccine of dendritic cells received by vein (IV) about 4 hours after T-cells and again on Day 21 (+/- 7 days). Cyclophosphamide 60 mg/kg/d IV over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m\^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10\^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26.
Group C: Prior Treatment with BRAF Inhibitor
EXPERIMENTALChemotherapy and IL-2 plus T-cells and the vaccine of dendritic cells received by vein (IV) about 4 hours after T-cells and again on Day 21 (+/- 7 days). Cyclophosphamide 60 mg/kg/d IV over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m\^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10\^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26.
Group D: Leptomeningeal Disease
EXPERIMENTALT-cells: 5.0x109 TIL administered on Day 1 and 10x109 TIL on Day 15. IL-2: 1.2 MIU of IL- 2 on Days 2, 4, 9, 11, 16 and 18 as tolerated. After this period, patient receives twice weekly IL-2 that will be gradually changed to weekly IL-2. After 4-6 weeks, patients switched to IL-2.
Group E: Chemotherapy + IL-2 plus T-Cells + Vaccine
EXPERIMENTALChemotherapy and IL-2 plus T-cells and the vaccine of dendritic cells received by vein (IV) about 4 hours after T-cells and again on Day 21 (+/- 7 days). Cyclophosphamide 60 mg/kg/d IV over 2 hours Days -7 and -6 (with Mesna) and Fludarabine 25 mg/m\^2 IV daily Days -5 to -1 before T cell infusion. On Day 0, up to 1.5 x 10\^11 T cells IV infusion over 30-60 minutes. Interleukin-2 12-16 hours after T cell infusion at standard dose of 720,000 IU/kg as intravenous bolus over 15 minute period every 8-16 hours for up to 15 doses on Days 1-5 and 22-26.
Interventions
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.
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.
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.
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
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.
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.
Eligibility Criteria
You may qualify if:
- Patients must have metastatic melanoma, uveal melanoma or stage III in-transit or regional nodal disease. (Turnstile I)
- Patients must receive an MRI/CT of the brain or PET/CT within 6 months of consenting. If new lesions are present, PI or his designee should make final determination regarding enrollment. (Turnstile I)
- Age greater than or equal to 12 years. (Turnstile I)
- Clinical performance status of ECOG 0-2. (Turnstile I)
- Patients previously treated with immunotherapy, targeted therapy, or no therapy will be eligible. Patients receiving cytotoxic agents will be evaluated by the PI or his designee as to suitable eligibility. (Turnstile I)
- Patients must have adequate TIL available. (Turnstile II)
- Patients must have a documented negative pregnancy test (urine or serum) for women who have menstruation in the past 12 months and without sterilization surgery.
- Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study such as: condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control. (Turnstile II)
- Pregnancy testing will be performed within 7 days prior to treatment. (Turnstile II)
- Hemoglobin greater than or equal to 8.0 g/dl. (Turnstile II - Chemotherapy/Cell Infusion).
- Patients in Cohort A will be randomized to receive either TIL alone or TIL plus Dendritic cells.
- Patients must be receiving a B-RAF inhibitor and failed to achieve PR or CR or have progressive disease in response to B-RAF treatment (Cohort C).
- i. Patients with MRI evidence of LMD, with or without evidence of malignant cells in CSF ("positive cytology"), or ii. Patients with evidence of malignant cells in the CSF (positive cytology), with or without MRI evidence of LMD, or iii. Patients with surgically-proven LMD (leptomeningeal involvement on pathology review) +/- MRI or CSF evidence by MRI or CSF cytology (Cohort D)
- a. Many patients present with concomitant systemic disease outside of the central nervous system. Extra-CNS disease status should meet the following criteria: i. Patients with concomitant systemic disease under control with current or prior systemic treatment, as per primary treating physician ii. Patients without any evidence of systemic disease, either receiving systemic treatment or on active observation (Cohort D)
- c. Previous Therapies i. Patients who are currently being treated with IT IL-2 for LMD are eligible. No wash out period is required. ii. Patients who have been previously treated with other IT therapies are eligible, as long as there is at least a 2 week wash out period iii. Patients who have previously received therapy with systemic TIL therapy are eligible.
- +2 more criteria
You may not qualify if:
- Has had prior systemic cancer cytotoxic chemotherapy within the past four weeks at the time of the start of the lymphodepletion regimen.
- Has had prior B-RAF or MEK targeted therapy within 7 days prior to the start of the lymphodepletion regimen (Cohort A and Cohort B).
- Achieves PR or CR in response to B-RAF treatment (Cohort C).
- Patients with rapidly advancing systemic disease, especially those without good options of systemic treatment for their disease outside the CNS. (Cohort D)
- Patients with rapidly advancing parenchymal brain metastases (Cohort D)
- Pregnant patients (Cohort D)
- Patients with rapid decline in neurological function as documented on exam and/or as per clinical judgment of treating physician (Cohort D)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Prometheus Laboratoriescollaborator
- Key Biologics, LLCcollaborator
- National Cancer Institute (NCI)collaborator
- Adelson Medical Researchcollaborator
Study Sites (1)
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
Saberian C, Amaria RN, Najjar AM, Radvanyi LG, Haymaker CL, Forget MA, Bassett RL, Faria SC, Glitza IC, Alvarez E, Parshottam S, Prieto V, Lizee G, Wong MK, McQuade JL, Diab A, Yee C, Tawbi HA, Patel S, Shpall EJ, Davies MA, Hwu P, Bernatchez C. Randomized phase II trial of lymphodepletion plus adoptive cell transfer of tumor-infiltrating lymphocytes, with or without dendritic cell vaccination, in patients with metastatic melanoma. J Immunother Cancer. 2021 May;9(5):e002449. doi: 10.1136/jitc-2021-002449.
PMID: 34021033DERIVEDJoseph RW, Peddareddigari VR, Liu P, Miller PW, Overwijk WW, Bekele NB, Ross MI, Lee JE, Gershenwald JE, Lucci A, Prieto VG, McMannis JD, Papadopoulos N, Kim K, Homsi J, Bedikian A, Hwu WJ, Hwu P, Radvanyi LG. Impact of clinical and pathologic features on tumor-infiltrating lymphocyte expansion from surgically excised melanoma metastases for adoptive T-cell therapy. Clin Cancer Res. 2011 Jul 15;17(14):4882-91. doi: 10.1158/1078-0432.CCR-10-2769. Epub 2011 Jun 1.
PMID: 21632855DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rodabe N. Amaria, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 10, 2006
First Posted
June 20, 2006
Study Start
February 1, 2006
Primary Completion (Estimated)
February 28, 2030
Study Completion (Estimated)
February 28, 2030
Last Updated
March 20, 2026
Record last verified: 2026-03