Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma
NCT ID: NCT00338377
Last Updated: 2025-10-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
1230 participants
INTERVENTIONAL
2006-02-01
2030-02-28
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Group A: Chemotherapy + IL-2 plus T-cells
Cyclophosphamide 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.
Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Fludarabine
25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
T-Cells
On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.
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.
Mesna
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
Group B: Chemotherapy + IL-2 plus T-Cells + Vaccine
Chemotherapy 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.
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.
Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Fludarabine
25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
T-Cells
On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.
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.
Mesna
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
Group C: Prior Treatment with BRAF Inhibitor
Chemotherapy 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.
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.
Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Fludarabine
25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
T-Cells
On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.
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.
Mesna
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
Group D: Leptomeningeal Disease
T-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.
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.
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.
Group E: Chemotherapy + IL-2 plus T-Cells + Vaccine
Chemotherapy 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.
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.
Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Fludarabine
25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
T-Cells
On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.
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.
Mesna
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
Interventions
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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.
Cyclophosphamide
60 mg/kg/d by vein over 2 hours on Days -7 and -6 before T cell infusion
Fludarabine
25 mg/m\^2 by vein daily over 30 minutes on Days -5 to -1 before T cell infusion.
T-Cells
On Days 0, up to 1.5 x 10\^11 T-cells by vein infusion over 30-60 minutes.
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.
Mesna
60 mg/kg with D5W or NS at 125 ml/hr infused intravenously over 24 hours on Day -7 and -6.
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.
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. 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)
3. Age greater than or equal to 12 years. (Turnstile I)
4. Clinical performance status of ECOG 0-2. (Turnstile I)
5. 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)
7. Patients must have adequate TIL available. (Turnstile II)
11. 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.
12. 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)
13. Pregnancy testing will be performed within 7 days prior to treatment. (Turnstile II)
17. Hemoglobin greater than or equal to 8.0 g/dl. (Turnstile II - Chemotherapy/Cell Infusion).
21. Patients in Cohort A will be randomized to receive either TIL alone or TIL plus Dendritic cells.
25. 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).
26. 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)
27. 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)
28. 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.
29. (contd #28) iv. Patients with VP shunts must have VP shunts with on/off valves and must be expected to tolerate VP shunt valve off for more than 6 hours Patients who have received CNS irradiation, including whole brain radiation or stereotactic radiosurgery, are eligible, if they are at least 1 weeks post CNS-irradiation (Cohort D)Patients who are currently being treated with IT IL-2 for LMD are eligible. No wash out period is required. (Cohort D)
30. d. Other Requirements i. Patients must be able to give informed consent ii. Patients must have ECOG performance status 0, 1 or 2 and/or KPS \> 50 iii. Patients must be able to swallow iv. Patients must be able to sit up with or without assistance v. Patients must be able to undergo contrast-enhanced MRI. (Cohort D)
Exclusion Criteria
2. 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).
4. Achieves PR or CR in response to B-RAF treatment (Cohort C).
10. Patients with rapidly advancing systemic disease, especially those without good options of systemic treatment for their disease outside the CNS. (Cohort D)
11. Patients with rapidly advancing parenchymal brain metastases (Cohort D)
12. Pregnant patients (Cohort D)
13. Patients with rapid decline in neurological function as documented on exam and/or as per clinical judgment of treating physician (Cohort D)
12 Years
ALL
No
Sponsors
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Prometheus Laboratories
INDUSTRY
Key Biologics, LLC
INDUSTRY
National Cancer Institute (NCI)
NIH
Adelson Medical Research
UNKNOWN
M.D. Anderson Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Rodabe N. Amaria, MD
Role: PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center
Locations
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The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Countries
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References
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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.
Joseph 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.
Related Links
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University of Texas MD Anderson Cancer Center Website
Other Identifiers
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NCI-2012-01368
Identifier Type: REGISTRY
Identifier Source: secondary_id
2004-0069
Identifier Type: -
Identifier Source: org_study_id
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