Table 1 Current Trials with Tumor-infiltrating Lymphocytes in Melanoma Registered by ClinicalTrials.gov per March 2018
From: Adoptive transfer of tumor-infiltrating lymphocytes in melanoma: a viable treatment option
Trial | Institute | Phase | Estimated enrollment | Intervention | TIL product | Lymphodepletion regimen | IL-2 regimen | Disease Stage | Primairy Outcome Measures | Identification number |
|---|---|---|---|---|---|---|---|---|---|---|
a. Recruiting Trials | ||||||||||
Combined Therapy of Nivolumab and Adoptive T Cell Therapy in Metastatic Melanoma Patients: Pilot Study Phase I/II | Nantes University Hospital, Nantes, France Initiation 2018 | I/II | 11 | TIL + IL-2 + Nivo (3 mg/kg every 2 w until w52) | Cohort 1: 5 × 108 TIL (3 patients) Cohort 2: 1-20 × 109 TIL at 14 w and 18 w | Not described | 600,000 IU/kg/d for 5d | Stage IIIb, IIIc or IV melanoma | AE | NCT03374839 |
Phase I Study to Assess Feasibility and Safety of Adoptive Transfer of Autologous Tumor-infiltrating Lymphocytes in Combination With Interleukin-2 Followed by Nivolumab Rescue for Advanced Metastatic Melanoma | CHUV, Lausanne, Switzerland Initiation 2018 | I | 10 | Lymphodepletion + TIL + IL-2 +/− Nivo (3 mg/kg, every 2w max 24 months) rescue | Unspecified | Cy i.v. for 2d and Flu i.v. 5d (not otherwise specified) | HD IL-2 t.i.d. max 8 doses | Stage IV melanoma | Feasibility AE | NCT03475134 |
A Phase 2, Single-Center, Open Label Study of Autologous, Adoptive Cell Therapy Following a Reduced Intensity, Non-myeloablative, Lymphodepleting Induction Regimen in Metastatic Melanoma Patients | Sheba Medical Center, Israel Initiation 2017 | II | 30 | Lymphodepletion + TIL + IL-2 | Unspecified | Flu (25 mg/m2 for 3 d) + TBI (2 Gy as single treatment) | 720,000 IU/kg t.i.d.. until tolerable toxicity, max 10 doses | Measurable metastatic melanoma | ORR AE | NCT03166397 |
Phase Ib Trial of Pembrolizumab Administered in Combination With or Following Adoptive Cell Therapy- A Multiple Cohort Study; The ACTIVATE (Adoptive Cell Therapy InVigorated to Augment Tumor Eradication) Trial | Princes Margaret Cancer Centre, Canada Initiation 2017 | Ib | 24 | Cohort 1: Lymphodepletion + TIL + IL-2 + pembro (200 mg q 3 w) Cohort 2: Lymphodepletion + TIL + IL-2 + pembro (200 mg q 3 w) | 1 × 1010–1.6 × 1011 TILs | Cohort 1: Cy i.v. 60 mg/kg/d for 2d + Flu 25 mg/m2 for 5 d Cohort 2: Cy i.v. 30 mg/kg per day for 2 days | Cohort 1 + 2: 125,000 IU/kg s.c./d | Unresectable stage III/ IV melanoma or Platinum resistant ovarian cancer | AE | NCT03158935 |
A Pilot Clinical Trial Combining PD-1 Blockade, CD137 Agonism and Adoptive Cell Therapy for Metastatic Melanoma | Lee Moffitt Cancer Center, Florida, US Initiation 2016 | Pilot | 12 | Cohort 1 (1st 6 patients): Lymphodepletion + TIL + IL-2 Cohort 2 (2nd 6 patients): Pre-treatment nivo + lymphodepletion + TIL + IL-2 | Unspecified, outgrowth in 4–8 w with CD137 activating antibody | Cy 2 d beginning 3–6 w after tumor collection for TIL growth + Flu for 5 d | Unspecified | Unresectable cutaneous or mucosal stage III/IV melanoma | AE Feasibility | NCT02652455 |
A Prospective Randomized and Phase 2 Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab | NIH Clinical Center, Bethesda, Maryland, US Initiation 2015 | II | 170 | Cohort 1 Arm 1 Anti-PD1/PD-L1 refractory patients: Lymphodepletion + TIL + IL-2 Cohort 1 Arm 2 Anti-PD1/PD-L1 refractory patients: Lymphodepletion + Pembro 2 mg/kg i.v. on d − 2, (and d 21 (+/−  2 d), 42 (+/−  2 d), and 63 (+/−  2 d) following cell infusion) + TIL + IL-2 Cohort 2 Arm 3 Anti-PD1/PD-L1 naive patients: Lymphodepletion + Pembro 2 mg/kg i.v. on d-2 (and days 21 (+/−  2 d), 42 (+/−  2 d), and 63 (+/−  2 d)) following cell infusion + TIL + IL-2 Cohort 1 Arm 1 (Retreatment) Anti-PD1/PD-L1 refractory patients with no response to study treatment or PD after PR/CR: Pembro 2 mg/kg i.v. on d − 2, and d 21 (+/−  2 d), 42 (+/−  2 d), and 63 (+/−  2 d) | Young TIL, not otherwise specified | Cohort 1 + 2: Cy 60 mg/kg i.v. for 2d + Flu 25 mg/m2for 5d | Cohort 1 + 2: 720,000 IU/kg i.v. t.i.d., max 12 doses | Measurable metastatic melanoma | ORR | NCT02621021 |
A Phase 2, Multicenter Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Treatment of Patients With Metastatic Melanoma | Iovance Investigative Site, Los Angeles, California, US Initiation 2015 | II | 60 | Cohort 1: Lymphodepletion + TIL + IL-2 Cohort 2: Lymphodepletion + TIL + IL-2 Cohort 3: re-treatment lymphodepletion + TIL + IL-2 | Cohort 1: LN-144 autologous TIL non-cryopreserved product Cohort 2: LN-144 autologous TIL cryopreserved Cohort 3: LN-144 autologous TIL re-treatment for 2nd LN-144 infusion | Lymphodepleting chemotherapy, not otherwise specified | Unspecified | Unresectable metastatic melanoma | ORR | NCT02360579 |
A Pilot Study of Lymphodepletion Plus Adoptive Cell Transfer With T-Cells Transduced With CXCR2 and NGFR Followed by High Dose Interleukin-2 in Patients With Metastatic Melanoma | MD Anderson Cancer Center, Houston, Texas, US Initiation 2015 | Pilot | 15 | Lymphodepletion + transduced TIL + IL-2 | Up to 1.5 × 1011 TIL (CXCR2 and NGFR transduced TIL) | Cyc 60 mg/kg for 2d + Flu 25 mg/m2for 5d | 720,000 IU/kgi.v. every 8–16 h, max 15 doses | Metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease | AE | NCT01740557 |
T-cell Therapy in Combination With Vemurafenib for Patients With BRAF Mutated Metastatic Melanoma | CCIT, Copenhagen, Herlev, Denmark Initiation 2014 | I/II | 12 | Vem 960 b.i.d. 7d before tumor harvest until lymphodepletion (d − 8) + TIL + IL-2 | 4-6 weeks culture time Infusion 1 × 109-2 × 1011 TIls | Cy 60 mg/kg for 2d + Flu 25 mg/m2 for 5 d | Decrescendo regimen (18 MIU/m2 for 6 h, 18 MIU/m2 for 12 h, 18 MIU/m2 for 24 h followed by 4,5 MIU/m2 for another 3 × 24 h) | Unresectable stage III/IV melanoma | AE | NCT02354690 |
Randomized Phase III Study Comparing a Non-myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Tumor Infiltrating Lymphocytes and Interleukin-2 to Standard Ipilimumab Treatment in Metastatic Melanoma | CCIT, Copenhagen, Herlev, Denmark NKI, Amsterdam, Netherlands Initiation 2014 | III | 168 | Cohort 1: Ipi 4 cycles (i.v. 3 mg/kg q 3 weeks) Cohort 2: Lymphodepletion + TIL + IL-2 | Unspecified | Cy 60 mg/kg iv for 2d + Flu 25 mg/m2 for 5d | 600,000 IU/kg t.i.d., max 15 doses | Unresectable stage III/IV melanoma | PFS | NCT02278887 |
A Pilot Study of Lymphodepletion Plus Adoptive Cell Transfer With TGF-beta Resistant (DNRII) and NGFR Transduced T-Cells Followed by High Dose Interleukin-2 in Participants With Metastatic Melanoma | MD Anderson Cancer Center, Houston, Texas, US Initiation 2014 | Pilot | 15 | Lymphodepletion + transduced TIL + IL-2 | Transduced DNRII TIL, equal number of transduced NGFR TIL, up to a total of 1.5 × 1011 TIL | Cy 60 mg/kg i.v. for 2d + Flu 25 mg/m2 i.v. for 5d | 720,000 IU/kg i.v. every 8–16 h max 15 doses on d 1–5 + 22–26 | Metastatic melanoma or stage III in-transit, subcutaneous, or regional nodal disease (turnstile I) | Feasibility | NCT01955460 |
A Phase II Study for Metastatic Melanoma Using High Dose Chemotherapy Preparative Regimen Followed by Cell Transfer Therapy Using Tumor Infiltrating Lymphocytes Plus IL-2 With the Administration of Pembrolizumab in the Retreatment Arm | NIH, Bethesda, Maryland, US Initiation 2013 | II | 64 | Cohort 1: Lymphodepletion + TIL + IL-2 Cohort 2 Retreatment Arm: 4 doses pembro Non-responders of patients with PR/CR and progress with prior pembro/nivo treatment may receive a second treatment. D 0 (2–4 d after last dose of flu), Pembro 2 mg/kg i.v. +/−  4 h prior to cell infusion. D 21 (+/−  2 d) following cell infusion, Pembro 2 mg/kg i.v. D 42 (+/−  2 d) following cell infusion, Pembro 2 mg/kg IV. D 63 (+/−  2 d) following cell infusion, Pembro 2 mg/kg i.v. | Young TIL | Cy 60 mg/kg/day for 2 d + Flu 25 mg/m2 i.v. for 5 d | 720,000 IU/kg i.v. t.i.d., max 12 doses | Measurable metastatic melanoma | ORR | NCT01993719 |
A Phase I Study to Evaluate Safety, Feasibility and Immunologic Response of Adoptive T Cell Transfer With or Without Dendritic Cell Vaccination in Patients With Metastatic Melanoma | Karolinska University Hospital Stockholm, Sweden Initiation 2013 | I | 10 | Cohort 1: Lymphodepletion + TIL + IL-2 Cohort 2: Lymphodepletion + TIL + IL-2 + i.d. DC vaccinations with up to 1.5 × 107 DC pulsed with autologous tumor lysate and NY-ESO-1 peptide after completion of IL-2 | Up to 5 × 1010 TILs i.v. infusion | Cy 60 mg/kg i.v. (d − 7&-6) + Flu 25 mg/m2 i.v. (d − 5 to − 1) | 100,000 IU/kg t.i.d., maximum 14 doses | Inoperable stage III or stage IV melanoma | Safety | NCT01946373 |
Phase II Study Evaluating The Infusion Of Autologous Tumor-Infiltrating Lymphocytes (TILs) And Low-Dose Interleukin-2 (IL-2) Therapy Following A Preparative Regimen Of Non-Myeloablative Lymphodepletion Using Cyclophosphamide And Fludarabine In Patients With Metastatic Melanoma | Princess Margaret Cancer Centre Toronto, Ontario, Canada Initiation 2013 | II | 12 | Lymphodepletion + TIL + IL-2 | 1 × 1010–1.6 × 1011 TILs | Cy 60 mg/kg i.v. for 2 d + Flu 25 mg/m2 i.v. for 5 d | 125,000 IU/kg/d for 2 w (2 d rest between each w) | Measurable, unresectable stage III/IV melanoma | ORR | NCT01883323 |
Lymphodepletion Plus Adoptive Cell Transfer With or Without Dendritic Cell Immunization in Patients With Metastatic Melanoma | MD Anderson Cancer Center Houston, Texas, US Initiation 2006 | II | 189 | Cohort 1: Lymphodepletion + TIL + IL-2 Cohort 2: Lymphodepletion + TIL infusion + IL-2 + 1 × 107–2.5 × 108 MART-1 peptide-pulsed DC i.v. Cohort 3 Prior treatment with BRAF-inhibitor: Lymphodepletion followed by TIL + IL-2 + 1 × 107–2.5 × 108MART-1 peptide-pulsed DC i.v. Cohort 4 Leptomeningeal Disease: TIL d 1 + d 15 | Cohort 1–3: Up to 1.5 × 1011 TIL Cohort 4: 5.0 × 109 TIL on d 1 + 10 × 109TIL on d 15 | Cy 60 mg/kg for 2 d + Flu 25 mg/m2 for 5d | Cohort 1–3: 720,000 IU/kg every 8–16 h, max doses on d 1–5 + 22–26 (+/−  7 d), as tolerated Cohort 4: 1.2 MIU of IL- 2 on d 2, 4, 9, 11, 16 and 18 as tolerated. Subsequently 2×/w IL-2 to weekly IL-2. After 4–6 w IL-2 maintenance | Metastatic melanoma, uveal melanoma or stage III in-transit or regional nodal disease | ORR | NCT00338377 |
b. Trials not yet recruiting | ||||||||||
A Phase 2 Study to Evaluate the Efficacy and Safety of Adoptive Transfer of Autologous Tumor Infiltrating Lymphocytes in Patients With Metastatic Uveal Melanoma | UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, US Initiation 2018 | II | 59 | Lymphodepletion + TIL + HD IL-2 | 1 × 109 - 2 × 1011 TIL per current standard protocol | Cy and Flu (not otherwise specified) | 600,000 IU/kg t.i.d. max 6 doses | Measurable metastatic uveal melanoma | ORR | NCT03467516 |
A Randomised Phase II Study in Metastatic Melanoma to Evaluate the Efficacy of Adoptive Cellular Therapy With Tumor Infiltrating Lymphocytes (TIL) and Assessment of High Versus Low Dose Interleukin-2 | The Christie NHS Foundation Trust, Manchester, UK Initiation 2013 | II | 90 | Arm A: lymphodepletion + TIL + HD IL-2 Arm B: lymphodepletion + TIL + LD IL-2 | Unscpecified | Cy 60 mg/kg 2 d + Flu 25 mg/m25 d | Arm A: HD IL-2, max 12 doses Arm B: LD IL-2, max 12 doses | Metastatic melanoma | ORR | NCT01995344 |
c. Non-recruiting Trials | ||||||||||
T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma | CCIT, Copenhagen, Herlev, Denmark Initiation 2014 | I/II | 12 | Lymphodepletion + TIL + IL-2 + s.c. injections of peginterferon- α 3× (d − 2, d 7 and d 14) | 4-6 weeks culture time Maximum number of TILs | Cy 60 mg/kg i.v for 2d + Flu 25 mg/m2 i.v for 5d | Continuous infusion decrescendo regimen (18 MIU/m2 IL-2 over 6 h, 18 MIU/m2 IL-2 over 12 h, 18 MIU/m2 IL-2 over 24 h followed by 4.5 MIU/m2 IL-2 over 24 h for 3d | Unresectable stage III/IV melanoma | AE | NCT02379195 |
Cellular Adoptive Immunotherapy Using Autologous Tumor-infiltrating Lymphocytes Following Lymphodepletion With Cyclophosphamide and Fludarabine for Patients With Metastatic Melanoma | University of Washington Cancer Consortium, Seattle, Washington, US Initiation 2013 | II | 13 | Lymphodepletion + TIL + IL-2 | Unspecified | Cy for 2d + Flu for 5d (not otherwise specified) | Unspecified | Stage III/IV melanoma | ORR | NCT01807182 |
Co-stimulation With Ipilimumab to Enhance Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma | Moffitt Cancer Center and Research Institute, Tampa, Florida, US Initiation 2012 | Pilot | 13 | Pre-treatment with ipi (cycle 1) prior to surgery to retrieve TILs. Cycle 2 of ipi 1 w after surgery (3 w after 1st cycle) followed by Lymphodepletion + TIL + IL-2 | 6 weeks outgrowth | Cy for 2d + Flu for 5d (not otherwise specified) | HD IL-2, otherwise unspecified. T.i.d., max 15 doses | Unresectable stage III/IV melanoma | Safety Feasibility | NCT01701674 |
Phase II Clinical Trial of Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma | Moffitt Cancer Center and Research Institute, Tampa, Florida, US Initiation 2012 | II | 17 | Vem (3w prior to TIL + post TIL for 2 yr) followed by Lymphodepletion + TIL infusion + IL-2 | Unspecified | Cy for 2d + Flu for 5d (not otherwise specified) | HD IL-2 (not otherwise specified) | Unresectable metastatic stage IV melanoma or stage III intransit or regional nodal disease | ORR Dropout rate | NCT01659151 |
Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltratring Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI) | NIH, Bethesda, Maryland, US Initiation 2011 | II | 102 | Cohort 1: Lymphodepletion + TIL + IL-2 Cohort 2: Lymphodepletion followed by TBI + TIL + IL-2 | Cohort 1 + 2: 1 × 109-2 × 1011young TILs | Cohort 1 + 2: Cy 60 mg/kg for 2 d + Flu 25 mg/m2 for 5 d Cohort 2: 2Gy of TBI 2×/day for 3d (total dose 12Gy) 3d prior to TIL infusion | Cohort 1 + 2: 720,000 IU/kg i.v. t.i.d., max 15 doses | Measurable metastatic melanoma | ORR | NCT01319565 |
Lymphodepletion Plus Adoptive Cell Transfer With High Dose IL-2 in Patients With Metastatic Melanoma | Moffitt Cancer Center, Tampa, Florida, US Initiation 2009 | I/II | 19 | Lymphodepletion + TIL + IL-2 | Unspecified | Cyc 60 mg/kg for 2d + Flu 25 mg/m2 for 5d | 720,000 IU/kg i.v. t.i.d max 15 doses | Unresectable stage III/IV melanoma | Feasibility | NCT01005745 |