Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: H. Lee Moffitt Cancer Center and Research Institute
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial is testing a new treatment that uses a patient's own immune cells, grown in a lab, to fight advanced melanoma that cannot be removed by surgery or has spread. The goal is to see if this approach is safe and effective. Using a patient's own immune cells to fight cancer has shown promise in treating advanced melanoma.
What evidence supports the effectiveness of the treatment TBio-4101 + Chemo + IL-2 for skin cancer?
Research shows that tumor-infiltrating lymphocytes (TILs) combined with interleukin-2 (IL-2) can lead to tumor regression in melanoma, a type of skin cancer. This suggests that the combination of TILs and IL-2, as part of the treatment, may be effective in treating skin cancer.
5891011Will I have to stop taking my current medications?
The trial requires that any systemic therapy, including anti-cancer monoclonal antibodies, must be stopped at least 4 weeks before starting the lymphodepleting therapy. Additionally, participants taking systemic steroid therapy or immunosuppressive medications are excluded from the trial.
How is the TBio-4101 + Chemo + IL-2 treatment for skin cancer different from other treatments?
This treatment is unique because it combines TBio-4101, a form of interleukin-2 (a protein that boosts the immune system), with chemotherapy and tumor-infiltrating lymphocytes (TILs), which are immune cells that target cancer cells. This combination aims to enhance the body's immune response against skin cancer, potentially offering greater effectiveness than using these components separately.
125811What safety information is available for the combination of TBio-4101, chemotherapy, and IL-2 in treating skin cancer?
Interleukin-2 (IL-2) has been studied extensively and is known to cause reversible but often severe side effects, such as low blood pressure, swelling, and kidney issues, especially at higher doses. These side effects require careful monitoring and supportive care in a critical-care setting. Other common side effects include fever, fatigue, nausea, and muscle pain, but these are generally manageable and reversible.
34567Eligibility Criteria
This trial is for adults aged 18-75 with unresectable or metastatic melanoma, including various types like cutaneous and ocular melanoma. Participants must have adequate organ function, an ECOG status of 0 or 1, and be willing to practice birth control. Those with treated brain metastases, a negative pregnancy test (if applicable), and the ability to sign consent can join. Excluded are pregnant women, those with severe heart issues or immunodeficiency disorders, active infections requiring IV antibiotics, history of severe allergies to study drugs, certain lung function impairments, autoimmune diseases needing steroids in the past 6 months.Inclusion Criteria
I am willing and able to undergo a procedure to collect my blood cells.
I can carry out all my usual activities without help.
I am between 18 and 75 years old.
My organs and bone marrow are working well.
I am a woman who can have children and my pregnancy test is negative.
I have a tumor larger than 1 cm that can be surgically removed for TIL therapy.
I have enough stored TIL cells for TBio-4101 therapy after a pre-REP.
My melanoma cannot be removed by surgery and includes skin, mucosal, or eye melanoma.
Exclusion Criteria
I am not on steroids or immunosuppressive medications.
I have an autoimmune disease and have been on high-dose steroids in the last 6 months.
My heart's pumping ability is reduced, or I have slight limitations on physical activity.
My lung function tests show less than 60% of the expected values.
I have previously undergone cell therapy.
I am currently on IV antibiotics for an infection.
My tumor is causing blockage, bleeding, or might soon break through an organ.
I need ongoing blood thinner treatment that can't be stopped or switched to a specific type.
Participant Groups
The trial tests TBio-4101 therapy using tumor infiltrating lymphocytes after lymphodepleting chemotherapy followed by interleukin-2 (IL-2) in participants with advanced melanoma. It aims to assess if this approach is feasible and safe while also evaluating its effectiveness against the cancer.
1Treatment groups
Experimental Treatment
Group I: Infusion of TBio-4101 TILExperimental Treatment4 Interventions
TBio-4101 is a tumor-infiltrating lymphocyte (TIL) product: participants tumor tissue is surgically removed and immune T-cells are taken out of the tumor and multiplied, or grown, in the laboratory. TIL product infused intravenously over 20 to 30 minutes within 2 to 4 days after the last dose of fludarabine
Participants will also receive:
* Cyclophosphamide dose 60 mg/kg/day for 2 days administered IV in 250 mL dextrose 5% in water infused simultaneously with Mesna 15 mg/kg/day delivered over 1 hour per day for 2 days. Fludarabine 25 mg/m2/day is delivered by intravenous piggyback daily over 15-30 minutes for 5 days.
* Interleukin-2 (IL-2)- will be given to participants through IV after they receive the infusion of the TIL. IL-2 is administered at a dose of 600,000 IU/kg (based on actual body weight) IV every 8-12 hours beginning within 24 hours of TIL infusion for a maximum of 6 doses.
Interleukin-2 is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Aldesleukin for:
- Metastatic melanoma
- Metastatic renal cell carcinoma
🇪🇺 Approved in European Union as PROLEUKIN for:
- Metastatic renal cell carcinoma
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
Loading ...
Who is running the clinical trial?
H. Lee Moffitt Cancer Center and Research InstituteLead Sponsor
Turnstone Biologics, Corp.Industry Sponsor
References
Effective chemotherapy for melanoma after treatment with interleukin-2. [2019]Twenty patients with biopsy-proven metastatic malignant melanoma, previously treated with interleukin-2 (IL-2), received combination chemotherapy for progressive disease. Treatment included carmustine, cisplatin, dacarbazine, and tamoxifen (BCDT). Nausea was the most common toxicity (100%) and usually was mild. Persistent thrombocytopenia was the most frequent toxicity limiting further treatment. Eleven patients (55%) had an objective partial response, three patients (15%) had a minor response, and six patients (30%) had no change or progressive disease in response to this treatment. These results were comparable to the high response rates (21 of 40, 53%) achieved with BCDT in previously untreated patients with melanoma. It was concluded that prior therapy using IL-2 does not significantly alter the response rate of metastatic melanoma to BCDT, thus suggesting that immunomodulators (e.g., IL-2) and chemotherapeutic agents are not cross-resistant treatments.
Immunological properties of melanoma tumor-infiltrating lymphocytes before and after IL-2-based biotherapies. [2007]Immunological properties of melanoma TILs before and/or after IL-2-based biotherapies were investigated. TILs harvested before therapies, including those for adoptive transfer, proliferated well in culture with IL-2 and displayed cytotoxicity relatively restricted to autologous tumor cells. In contrast, TILs during or at the end of IL-2 based therapies did not proliferate in culture with IL-2. TILs from tumors even harvested 45 days after the end of IL-2 therapy modestly proliferated in culture with IL-2 and showed MHC-nonrestricted cytotoxicity. The number of live tumor cells that were yielded from melanomas during or at the end of IL-2-based therapies significantly decreased in all nine patients with metastatic melanomas, regardless of their clinical responses (2 PR, 2 MR, 2 SD, and 3 PD). Collectively, these results suggest that current IL-2-based therapies resulted in both transient nonresponsiveness of TILs to IL-2 and transient decrease in the number of live tumour cells in most melanoma patients.
The immunotherapy of human cancer with interleukin 2: present status and future directions. [2019]Interleukin-2 (IL-2) is the principal soluble factor responsible for the proliferation of activated T cells. In animal models and humans, administration of IL-2 can induce regressions of established cancers. These antitumor effects may be partially mediated by cytotoxic effector cells activated by IL-2, including lymphokine-activated killer (LAK) cells and cytotoxic T lymphocytes. IL-2 has additional effects on other components of the cellular immune system, including B cells and macrophages, and induces secretion of other soluble mediators, including tumor necrosis factors (TNF) alpha and beta, and interferon-gamma. These effects may contribute to the antitumor activity of IL-2 as well as its dose-related toxicity. Multiple Phase I and II trials have been completed or are ongoing evaluating the clinical and biological effects of IL-2 given by diverse routes and schedules, both alone and in combination with infusions of ex vivo IL-2-activated autologous LAK cells. Other studies have begun to explore the potential for antitumor synergy when IL-2 is combined with the different interferons, TNF, monoclonal antibodies, and cytotoxic drugs. The biology, toxicity, and clinical activity documented in IL-2 clinical trials to date are reviewed, and prospects for future directions outlined.
Recombinant interleukin-2: a biological response modifier. [2007]The chemical properties, pharmacology, immunology, pharmacokinetics, clinical trials, adverse effects, and dosage and administration of recombinant interleukin-2 are reviewed. Recombinant interleukin-2 is an immunomodulating agent that stimulates the proliferation, activation, and differentiation of T and B cells, natural killer cells, and thymocytes. Two recombinant interleukin-2 products, aldesleukin and teceleukin, have been extensively studied. Most clinical experience with recombinant interleukin-2 has involved the treatment of renal cell carcinoma, melanoma, and colorectal cancer with a National Cancer Institute protocol. Patients with renal cell cancer and melanoma, who historically respond poorly to conventional therapy, have responded to therapy with recombinant interleukin-2. Recombinant interleukin-2 has been administered alone and in combination with lymphokine-activated killer cells, tumor-infiltrating lymphocytes, and interferons alfa and beta. In addition, the effect of dosage, administration rate, dosage schedule, route of administration, and cyclophosphamide pretreatment have been investigated. The adverse effects of recombinant interleukin-2 are generally reversible but are frequently severe and dose-related. Dose-limiting adverse effects include hypotension, edema, and renal dysfunction. Since hemodynamic monitoring and supportive care are essential, recombinant interleukin-2 should be administered in a critical-care setting by trained personnel. Recombinant interleukin-2 represents an advance in the therapy of renal cell cancer and melanoma and offers a new approach to the treatment of other refractory or recurrent malignancies.
Interleukin-2 alone and in combination with other cytokines in melanoma: the investigational approach at the University of Texas M.D. Anderson Cancer Center. [2019]The clinical data that have been accumulated so far suggests a significant influence of IL-2 dose and schedule on the immunobiological effects and clinical toxicities observed with this cytokine. Consequently, the series of Phase I and Phase II clinical trials conducted at the University of Texas M. D. Anderson Cancer Center in patients with advanced malignant melanoma investigating the use of IL-2 in combination with other cytokines, monoclonal antibodies, or ex vivo activated effector cells have used a common dose and schedule of IL-2 administration for which abundant immunobiological information already exists. This approach allows cross-trial comparison of experience with toxicities, immunobiological observations and clinical activity by a group of investigators within a single institution, and more rapid and valid evolution towards combination biological therapy, which preclinical data suggest will have greater activity than single agent therapy.
A phase I clinical trial of recombinant interleukin-2 by periodic 24-hour intravenous infusions. [2017]Recombinant interleukin-2 (rIL-2) (NSC# 600664; Hoffmann-La Roche, Inc., Nutley, NJ) was studied in a phase I clinical trial in 33 patients with advanced, measureable cancer of the colon or malignant melanoma, Eastern Cooperative Oncology Group (ECOG) performance status O-1, and no prior chemotherapy or radiotherapy. The goal of the study was to identify a dose and schedule of IL-2 to generate maximal immune modulation with tolerable toxicity. Such a regimen might allow the addition of other treatment modalities and/or prolonged treatment duration in later trials. Each patient received IL-2 as a continuous 24-hour infusion once weekly for 4 weeks and then twice weekly for 4 weeks. Five treatment groups received from 10(3) U/m2 to 3 x 10(7) U/m2 per 24-hour infusion. The maximal tolerated dose was 3 x 10(7) U/m2/d twice weekly. Patients treated twice weekly at 1 x 10(7) and 3 x 10(7) U/m2/d had immune modulation in terms of lymphocytosis, eosinophilia, increased natural killer (NK) activity, and elevated numbers of peripheral blood mononuclear cells expressing CD16, OKT10/Leu-17, and Leu-19 surface markers. Endogenous generation of peripheral blood lymphokine-activated killer (LAK) activity was demonstrated by lysis of NK-resistant Daudi targets, in patients treated at 3 x 10(7) U/m2/d. Biochemical and hematological abnormalities were moderate and reversible. Clinical toxicity included hypotension, myalgia, arthralgia, stomatitis, fever, fatigue, nausea, headache, chills, diarrhea, and oliguria at high doses. Cardiovascular toxicity was tolerable for most patients and reversed after IL-2 was stopped. Two of six melanoma patients at 3 x 10(7) U/m2/d achieved partial responses by the end of the eighth week. This IL-2 schedule appears to produce potentially clinically useful immune enhancement with tolerable toxicity.
In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2. [2019]A phase-I study of the recombinant, non-mutagenized interleukin 2 (rIL2, BioleukinTM) was performed in 12 melanoma patients (Pts). From 100 to 800 micrograms/m2 of rIL2 were administered by i.v. bolus injection, TID for 4-8 days. Side-effects included fever, malaise, low serum K+ and Ca++ values, electrocardiographic abnormalities, leukopenia and thrombocytopenia. No major organ toxicity and no significant fluid retention were observed at the administered doses. Treatment induced a rapid depletion of peripheral blood lymphocytes (PBL) with a rebound (2-6 times the pre-treatment values), 24-48 hr after rIL2 discontinuation. PBL obtained between the 5th treatment day and the 2nd post-treatment day showed: (a) enhanced proliferation (II/12 Pts) with stimulation indexes of 6-52; (b) increased cytotoxicity against autologous tumor cells (2/2 Pts), allogeneic melanomas (5/7 Pts), the Daudi (5/6 Pts) and K562 cell lines (7/12 Pts); and (c) increased expression of IL2 receptors (8/12 Pts) and of DR antigens (6/12 Pts). Lymphocytes collected 1-2 days after treatment and activated in vitro with rIL2 showed a more rapid development of tumor cytotoxicity, with an earlier loss of activity. Spontaneous proliferation, autologous or allogeneic tumor cytotoxicity and expression of IL2 receptors obtained after in vivo treatment with rIL2 were significantly weaker than those induced during in vitro stimulation. No major objective responses were detected in these patients.
Enhanced interleukin-2 production in human tumor-infiltrating lymphocytes engineered by 3'-truncated interleukin-2 gene. [2019]Tumor-infiltrating lymphocytes (TILs), T lymphocytes associated with solid tumors that can be grown with interleukin (IL)-2 in vitro, preferentially accumulate at tumor sites after adoptive transfer. Therefore, TILs can be considered for use as cellular vehicles in gene therapy. We transduced melanoma TILs with the IL-2 gene and clarified functional characteristics of the TIL transductants. TILs transduced with 3'-end-truncated IL-2 gene (480 bp) produced high amounts of IL-2 detected in supernatants when compared to TILs transduced with the native IL-2 gene containing 3'-end adenine-thymidine (AT)-rich sequences (650 bp). The level of IL-2 in supernatants was higher with the addition of anti-Tac antibody (Ab) to block the consumption of IL-2 by the TILs. These TILs could proliferate autonomously in the absence of exogenous IL-2, and the proliferation of TILs could be completely blocked by anti-IL-2 Ab or anti-IL-2 receptor Ab. Thus TILs transduced with IL-2 gene can proliferate through the autocrine loop. However, the expression of IL-2 from TILs transduced with the IL-2 gene was downregulated after 2 to 3 weeks of G418 selection. Our study indicates the feasibility of transduction and expression of a truncated 480-bp IL-2 gene into TILs and the possibility of employing adoptive immunotherapy protocols using TILs modified with this IL-2 gene.
Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. [2021]Adoptive cell therapy (ACT) with autologous tumor-infiltrating lymphocytes (TILs) and high-dose interleukin-2 (IL-2) administered to lymphodepleted patients with melanoma can cause durable tumor regressions. The optimal TIL product for ACT is unknown.
Pathologic complete response to intralesional interleukin-2 therapy associated with improved survival in melanoma patients with in-transit disease. [2015]Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response.
Tumor infiltrating lymphocytes as adjuvant treatment in stage III melanoma patients with only one invaded lymph node after complete resection: results from a multicentre, randomized clinical phase III trial. [2020]Adoptive tumor-infiltrating lymphocytes (TIL) therapy and interleukin-2 (IL-2) have been investigated in melanoma.